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This study is mainly based on T helper type 17 (Th17) cells analysis of the mechanism of prostaglandin E2 (PGE2) promoting the progression of dry eye (DE). Scopolamine and dry environment were used to induce mice DE model. Celecoxib was used to inhibit PGE2. Corneal epithelial cells and CD4+ T cells were used to construct a co-culture system. The osmotic pressure was increased by adding NaCl to simulate DE in vitro. AH6809 and E7046 were used to pre-culture to inhibit EP2/4 in T cells to verify the effect of exogenous PGE2 on Th17 cell differentiation and corneal epithelial cell apoptosis. The function of Th17 cells was analyzed by detecting RORγt and interleukin-17 (IL-17). PGE2 was instilled on the ocular surface to induce DE symptoms of mice. AH6809 and E7046 were used to inhibit EP2/4. The corneal epithelial cell apoptosis was observed by TUNEL. The proportion of Th17 cells in corneal tissue and draining lymph nodes (DLNs) was detected by flow cytometry. In DE mice, the concentration of PGE2 and IL-17 increased in tears, and the proportion of Th17 increased, while inhibition of PGE2 alleviated the symptoms of DE and inhibited Th17 differentiation. Hypertonic environment induces corneal epithelial cells to secrete PGE2. PGE2 promoted the expression of EP2/4 and the differentiation of Th17 cells in vitro. The hypertonic environment promoted PGE2 level and the apoptosis of corneal epithelial cells in the co-culture system. PGE2 alone did not cause corneal epithelial cell apoptosis, while PGE2 promoted apoptosis by promoting Th17. Blocking EP2/4 reduced the induction of Th17 differentiation by PGE2 and the promoted corneal epithelial cell apoptosis. Animal experiments showed that exogenous PGE2 induced DE symptoms. Blocking EP2/4 not only inhibited the proportion of Th17, but also alleviated the apoptosis of corneal epithelial cells caused by PGE2. PGE2 induces aggravation of inflammation by promoting the level of Th17 in the ocular surface, and causes corneal epithelial cell apoptosis, thereby participating in the progression of DE. [Display omitted] • In DE mice, the concentration of PGE2 and IL-17, and the proportion of Th17. • PGE2 promotes Th17 cell differentiation in DE through EP2/4. • PGE2 participates in the progression of DE by promoting the differentiation of Th17 cells. [ABSTRACT FROM AUTHOR]

B Energy Storage Performance of Composite Films b In article number 2300233, Fei Yang, Zheng Yuan, Xianwei Wang, and co-workers prepare PbZr SB 0.52 sb Ti SB 0.48 sb O SB 3 sb /PbZrO SB 3 sb films using sol-gel method. Energy Storage Performance of PZT/PZ Composite Films Obtained by Sol-Gel Method The results show that the energy storage properties could be adjusted by the phase composition variation, and the optimal films annealed at 620 °C for 3 min obtain the high I W i SB I rec i sb of 10.0 J cm SP -3 sp and the I i of 84.8%. [Extracted from the article]

Disc degeneration is the common pathology underlying various degenerative spinal disorders and currently there is no effective cure. Here, we found nucleus pulposus (NP) cell senescence was closely associated with the severity of disc degeneration, and exosomes (Exos) derived from mesenchymal stem cells (MSCs) ameliorated NP cell senescence and promoted extracellular matrix (ECM) deposition. As chitosan-based hydrogels have been widely used as vehicles to deliver Exos due to their prominent antibacterial capacity, biocompatibility, and biodegradability, we developed an Exos-laden hydrogel based on quaternized chitosan (QCS) and oxidized starch (OST) to treat disc degeneration. The synthesized QCS-OST hydrogel is injectable, self-healing, biocompatible, and demonstrated desirable pore size, injectable properties, and sustainable release of Exos. In a rat model of disc degeneration, the QCS-OST/Exos hydrogel was able to rejuvenate NP cell senescence, promote ECM remodeling, and partially restore the structures of NP and annulus fibrosis. Our findings suggested that the novel QCS-OST/Exos hydrogel is an effective therapeutic strategy for treating disc degeneration via alleviating NP cell senescence. [ABSTRACT FROM AUTHOR]

New lanthanide coordination polymers (Ln-CPs), {[Ln(DPBA)(phen) 2 ]·2H 2 O} n (Ln = Eu 1 , Tb 2 , Gd 3), based on a ternary system containing 2-(3′,4′-dicarboxyphenoxy)-benzoic acid (H 3 DPBA) and 1,10-phenanthroline (phen) were hydrothermally prepared. The Ln-CPs exhibit a 1D structure with [LnO 4 N 4 ] polyhedra and DPBA ligands, which can be extended to a 3D supramolecular network by water clusters and π-stacking. The coordination polymers have remarkable thermal stability up to 340 °C and solvent stability (in various solvents containing water in the 3–12 pH range). 1 , 2 , 3 show bright red, green, and blue emissions, respectively. Notably, 1 exhibits a very high photoluminescence quantum yield (PLQY) of 86%, which is among the best values for Ln-CPs. Energy transfer analysis is performed for Ln-CPs by DFT/TD-DFT calculations, solid-state phosphorescence (77 K) and UV–vis absorption spectra of Gd-CP. Favorable photostability of 1 is observed through a UV aging experiment, which shows that the PLQY of 1 maintained 55% of its initial value after 150 h Ultraviolet A (UVA) irradiation, which makes it potentially useful as a light conversion material. In addition, the Gd 0.993 Eu 0.0017 Tb 0.0053 -CP codoped system shows white emission with a high PLQY of 35.09%, which is among the highly ranked as compared with reported white light emissions based on Ln-CPs. This highly luminescent Eu-CP can also be used as a sensitive fluorescence sensor for antibiotic detection in aqueous solution. Eu-CP and its isomorphic Tb/Gd-CPs were constructed from H 3 DPBA and phen ligands. Eu-CP has excellent photoluminescence quantum yield, remarkable thermal and solvent stabilities, and favorable photostability under UV irradiation. A highly efficient white lighting material was prepared through a Ln(III) ion doping strategy. Also, Eu-CP has high sensitivity for antibiotics detection in aqueous solution. [Display omitted] • 1D highly luminescent and stable Ln-CPs with DPBA and phen ligands were constructed. Eu-CP exhibits high PLQY (86%). • Eu-CP has remarkable thermally and solvent stabilities, and favorable photostability. • Doped Gd:Eu/Tb-CP shows efficient white light emission with high PLQY (35.09%). • Eu-CP can selectively detect MNZ, ONZ and RNZ in aqueous solution with high sensitivity. [ABSTRACT FROM AUTHOR]

We previously reported that major bovine milk oligosaccharides (BMO) can qualitatively and quantitatively analyzed using ultra high liquid chromatography on a high sensitivity fluorescence detection instrument; the method does not require the removal of lactose and uses small (only 100 μL) samples. In this study, we extended our strategy to fractionation and purification of BMO using membrane separation and chromatography techniques. The effects of membrane molecular weight cut-off (MWCO) and diafiltration the efficiency of the overall process were evaluated, with process optimization leading to suitable MWCOs for microfiltration (ceramic, 0.1 μm), ultrafiltration (spiral wound organic membrane, 30 kDa), and nanofiltration (spiral wound organic membrane, 500–700 Da). Total BMO recoveries of 97.36, 95.58, and 98.30% were observed for the microfiltration, ultrafiltration, and nanofiltration stages, respectively, with corresponding membrane fluxes of 75.74, 76.90, and 81.68 L/(m2·h), respectively. In addition, the crude BMOs were further purified using size-exclusion chromatography, activated charcoal, lactase digestion, dialysis, crystallization, and anion-exchange chromatography. Anion-exchange chromatography with Q Sepharose Fast Flow anion-exchange resin was found to be more suited to industrial BMO production than other methods; it not only effectively separates lactose and oligosaccharides, but also exhibits dynamic adsorption capacity of 1.20 mg BMOs /mL gel. [Display omitted] • Crude bovine milk Oligosaccharides (BMO) were successfully enriched by integrated membrane technology. • Low molecular weight lactose and BMO cannot be effectively separated by nanofiltration. • Q sepharose fast flow anion exchange resin is most suitable for further industrial purification of BMO. [ABSTRACT FROM AUTHOR]

Background The field of microbiota-gut-brain research in animals has progressed, while the exact nature of gut microbiota-brain-cognition relationship in humans is not completely elucidated, likely due to small sample sizes and single neuroimaging modality utilized to delineate limited aspects of the brain. We aimed to comprehensively investigate such association in a large sample using multimodal MRI. Methods Fecal samples were collected from 157 healthy young adults and 16S sequencing was used to assess gut microbial diversity and enterotypes. Five brain imaging measures, including regional homogeneity (ReHo) and functional connectivity density (FCD) from resting-state functional MRI, cerebral blood flow (CBF) from arterial spin labeling, gray matter volume (GMV) from structural MRI, and fractional anisotropy (FA) from diffusion tensor imaging, were jointly analyzed with a data-driven multivariate fusion method. Cognition was evaluated by 3-back and digit span tasks. Results We found significant associations of gut microbial diversity with ReHo, FCD, CBF, and GMV within the frontoparietal, default mode and visual networks, as well as with FA in a distributed set of juxtacortical white matter regions. In addition, there were FCD, CBF, GMV, and FA differences between Prevotella- versus Bacteroides-enterotypes in females and between Prevotella- versus Ruminococcaceae-enterotypes in males. Moreover, the identified neuroimaging fusion biomarkers could mediate the associations between microbial diversity and cognition. Conclusions Our findings not only expand existing knowledge of the microbiota-gut-brain axis, but also have potential clinical and translational implications by exposing the gut microbiota as a promising treatment and prevention target for cognitive impairment and related brain disorders. • Gut microbiota-brain-cognition association was assessed using multimodal MRI. • Multimodal MRI measures were jointly analyzed with a multivariate fusion method. • Gut microbial diversity was correlated with multiple neuroimaging fusion measures. • There were differences in multiple neuroimaging fusion measures between enterotypes. • Fusion biomarkers mediated the relations between microbial diversity and cognition. [ABSTRACT FROM AUTHOR]

Bovine milk oligosaccharides (BMOs) and human milk oligosaccharides (HMOs) have similar functions. In this investigation, a simple and rapid quantitative analysis method of UPLC for BMOs concentration was proposed, and the heat stability of BMOs was also revealed. BMOs were separated on an Acquity UPLC® Glycan BEH amide column (2.1 mm × 150 mm, 1.7 μm) using 100 m m ammonium formate (pH 4.5) and 100% acetonitrile as mobile phase for gradient elution at a flow rate of 0.45 mL min−1. The potential in quantification of BMOs were satisfactorily validated in terms of linearity (R2 ≥ 0.9992), repeatability and intermediate precision (RSD ≤ 4.46%), and spike recovery (≥90.27%). For all investigated oligosaccharides, LOD ranged from 1.97 to 9.38 μg L−1 and LOQ values ranged between 6.84 and 31.25 μg L−1. In addition, BMOs did not degrade after heating at 45–100 °C for 10–120 min. [ABSTRACT FROM AUTHOR]

Background: Gallbladder cancer (GBC) is the most malignant cancer occurring in the biliary tract cancer featured with undesirable prognosis, in which most patients die within a year of cholecystectomy. Long noncoding RNAs (lncRNAs) function as critical regulators of multiple stages of cancers. Herein, the mechanism of lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in GBC is investigated. Methods: Microarray-based analysis initially provided data suggesting that the expression of MALAT1 was up-regulated while that of the ABI family member 3 binding protein (ABI3BP) was down-regulated in GBC tissues and cell lines. Kaplan-Meier method was then adopted to analyze the relationship between the MALAT1 expression and overall survival and disease-free survival of patients with GBC. A set of in vitro and in vivo experiments were conducted by transducing ABI3BP-vector or sh-MALAT1 into GBC cells. Results: The results confirmed that the cancer prevention effects triggered by restored ABI3BP and depleted MALAT1 as evidenced by suppressed cell growth and enhanced cell senescence. MALAT1 was observed to down-regulate ABI3BP expression through recruitment of the enhancer of zeste homolog 2 (EZH2) to the ABI3BP promoter region while the silencing of MALAT1 or suppression of H3K27 methylation was observed to promote the expression of ABI3BP. Furthermore, GBC patients with high expression of MALAT1 indicated poor prognosis. Conclusion: The current study clarifies that MALAT1 silencing and ABI3BP elevation impede the GBC development through the H3K27 methylation suppression induced by EZH2, highlighting a promising competitive paradigm for therapeutic approaches of GBC. [ABSTRACT FROM AUTHOR]

Accurate recognition of nutritional components in food is crucial for dietary management and health monitoring. Current methods often rely on traditional chemical analysis techniques, which are time-consuming, require destructive sampling, and are not suitable for large-scale or real-time applications. Therefore, there is a pressing need for efficient, non-destructive, and accurate methods to identify and quantify nutrients in food. In this study, we propose a novel deep learning model that integrates EfficientNet, Swin Transformer, and Feature Pyramid Network (FPN) to enhance the accuracy and efficiency of food nutrient recognition. Our model combines the strengths of EfficientNet for feature extraction, Swin Transformer for capturing long-range dependencies, and FPN for multi-scale feature fusion. Experimental results demonstrate that our model significantly outperforms existing methods. On the Nutrition5k dataset, it achieves a Top-1 accuracy of 79.50% and a Mean Absolute Percentage Error (MAPE) for calorie prediction of 14.72%. On the ChinaMartFood109 dataset, the model achieves a Top-1 accuracy of 80.25% and a calorie MAPE of 15.21%. These results highlight the model's robustness and adaptability across diverse food images, providing a reliable and efficient tool for rapid, non-destructive nutrient detection. This advancement supports better dietary management and enhances the understanding of food nutrition, potentially leading to more effective health monitoring applications., Competing Interests: HT was employed by China Tea Technology Co., Ltd. FL was employed by Beijing Sanyuan Foods Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Tian, Ju, Ma, Yang, Chen and Liu.)

Freezing of gait (FOG) leads to an increased risk of falls and limited mobility in individuals with Parkinson's disease (PD). However, existing research ignores the fine-grained quantitative assessment of FOG severity. This paper provides a double-hurdle model that uses typical spatiotemporal gait features to quantify the FOG severity in patients with PD. Moreover, a novel multi-output random forest algorithm is used as one hurdle of the double-hurdle model, further enhancing the model's performance. We conduct six experiments on a public PD gait database. Results demonstrate that the designed random forest algorithm in the double-hurdle model-hyperparameter independence framework achieves outstanding performances with the highest correlation coefficient (CC) of 0.972 and the lowest root mean square error (RMSE) of 2.488. Furthermore, we study the effect of drug state on the gait patterns of PD patients with or without FOG. Results show that "OFF" state amplifies the visibility of FOG symptoms in PD patients. Therefore, this study holds significant implications for the management and treatment of PD.

Background: Evidence has established the prominent involvement of rapid eye movement (REM) sleep disturbance in major depressive disorder (MDD). However, the neural correlates of REM sleep in MDD and their clinical significance are less clear., Methods: Cross-sectional and longitudinal polysomnography and resting-state functional MRI data were collected from 131 MDD patients and 71 healthy controls to measure REM sleep and voxel-mirrored homotopic connectivity (VMHC). Correlation and mediation analyses were performed to examine the associations between REM sleep, VMHC, and clinical variables. Moreover, we conducted spatial correlations between the neural correlates of REM sleep and a multimodal collection of reference brain maps to facilitate genetic, structural and functional annotations., Results: MDD patients exhibited REM sleep abnormalities manifesting as higher REM sleep latency and lower REM sleep duration, which were correlated with decreased VMHC of the precentral gyrus and inferior parietal lobe and mediated their associations with more severe anxiety symptoms. Longitudinal data showed that VMHC increase of the inferior parietal lobe was related to improvement of depression symptoms in MDD patients. Spatial correlation analyses revealed that the neural correlates of REM sleep in MDD were linked to gene categories primarily involving cellular metabolic process, signal pathway, and ion channel activity as well as linked to cortical microstructure, metabolism, electrophysiology, and cannabinoid receptor., Conclusion: These findings may add important context to the growing literature on the complex interplay between sleep and MDD, and more broadly may inform future treatment for depression via regulating sleep., Competing Interests: Declaration of competing interest All the authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Gastrointestinal tumors, the second leading cause of human mortality, are characterized by their association with inflammation. Currently, progress in the early diagnosis and effective treatment of gastrointestinal tumors is limited. Recent whole-genome analyses have underscored their profound heterogeneity and extensive genetic and epigenetic reprogramming. Epigenetic reprogramming pertains to dynamic and hereditable alterations in epigenetic patterns, devoid of concurrent modifications in the underlying DNA sequence. Common epigenetic modifications encompass DNA methylation, histone modifications, noncoding RNA, RNA modifications, and chromatin remodeling. These modifications possess the potential to invoke or suppress a multitude of genes associated with cancer, thereby governing the establishment of chromatin configurations characterized by diverse levels of accessibility. This intricate interplay assumes a pivotal and indispensable role in governing the commencement and advancement of gastrointestinal cancer. This article focuses on the impact of epigenetic reprogramming in the initiation and progression of gastric cancer, esophageal cancer, and colorectal cancer, as well as other uncommon gastrointestinal tumors. We elucidate the epigenetic landscape of gastrointestinal tumors, encompassing DNA methylation, histone modifications, chromatin remodeling, and their interrelationships. Besides, this review summarizes the potential diagnostic, therapeutic, and prognostic targets in epigenetic reprogramming, with the aim of assisting clinical treatment strategies., Competing Interests: The authors declare no conflict of interests., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

The identification of aging- and longevity-associated genes is important for promoting healthy aging. By analyzing a large cohort of Chinese centenarians, we previously found that single-nucleotide polymorphisms (SNPs) in the SLC39A11 gene (also known as ZIP11 ) are associated with longevity in males. However, the function of the SLC39A11 protein remains unclear. Here, we found that SLC39A11 expression is significantly reduced in patients with Hutchinson-Gilford progeria syndrome (HGPS). In addition, we found that zebrafish with a mutation in slc39a11 that significantly reduces its expression have an accelerated aging phenotype, including a shortened average lifespan, muscle atrophy and reduced swimming, impaired muscle regeneration, gut damage, and abnormal morphology in the reproductive system. Interestingly, these signs of premature aging were more pronounced in male zebrafish than in females. RNA-sequencing analysis revealed that cellular senescence may serve as a potential mechanism for driving this slc39a11 deficiency-induced phenotype in mutant zebrafish. Moreover, immunofluorescence showed significantly increased DNA damage and reactive oxygen species signaling in slc39a11 mutant zebrafish. Using inductively coupled plasma mass spectrometry (ICP-MS), we found that manganese significantly accumulates in slc39a11 mutant zebrafish, as well as in the serum of both global Slc39a11 knockout and hepatocyte-specific Slc39a11 knockout mice, suggesting that this metal transporter regulates systemic manganese levels. Finally, using cultured human fibroblasts, we found that both knocking down SLC39A11 and exposure to high extracellular manganese increased cellular senescence. These findings provide compelling evidence that SLC39A11 serves to protect against the aging process, at least in part by regulating cellular manganese homeostasis., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Zhidan Xia et al.)

Background and Purpose: Clinical studies showed that prolonged infusion of methotrexate (MTX) leads to more severe adverse reactions than short infusion of MTX at the same dose. We hypothesized that it is the saturation of folate polyglutamate synthetase (FPGS) at high MTX concentration that limits the intracellular synthesis rate of methotrexate polyglutamate (MTX-PG). Due to a similar accumulation rate, a longer infusion duration may increase the concentration of MTX-PG and, result in more serious adverse reactions. In this study, we validated this hypothesis., Experimental Approach: A549, BEL-7402 and MHCC97H cell lines were treated with MTX at gradient concentrations. Liquid chromatograph-mass spectrometer (UPLC-MS/MS) was used to quantify the intracellular concentration of MTX-PG and the abundance of FPGS and γ-glutamyl hydrolase (GGH). High quality data were used to fit the cell pharmacokinetic model., Key Results: Both cell growth inhibition rate and intracellular MTX-PG concentration showed a nonlinear relationship with MTX concentration. The parameter Vmax in the model, which represents the synthesis rate of MTX-PG, showed a strong correlation with the abundance of intracellular FPGS., Conclusion and Implications: According to the model fitting results, it was confirmed that the abundance of FPGS is a decisive factor limiting the synthesis rate of MTX-PG. The proposed hypothesis was verified in this study. In addition, based on the intracellular metabolism, a reasonable explanation was provided for the correlation between the severity of adverse reactions of MTX and infusion time. This study provides a new strategy for the individualized treatment and prediction of efficacy/side effects of MTX., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Member of the V-type ATPase family have attracted vast attention in tumor progression. Nevertheless, the specific member of V-ATPase, ATP6V1C2, its regulatory function in colorectal cancer (CRC) progression was poorly understood. In this study, comprehensive analyses demonstrated the role of ATP6V1C2 in CRC progression and drug screening based on ATP6V1C2 was carried out. As a result, among the ATPV1s family, ATP6V1C2 was significantly highly expressed in CRC. Immuno-infiltration analysis suggests that, the interaction between CRC cells and immune cells resulting in reduced immune and estimate scores. GSEA analysis found that, ATP6V1C2 negatively correlates with immune cells，especially CD8T cells. Next, Ecotyper database queries indicated that ATP6V1C2 was negatively correlates with characteristic gene expression in CD8T cells. Then, COX regression analysis and survival curves made it clear that ATP6V1C2 is positively correlates with clinicopathological progression leading to poor CRC prognosis. CellMiner explore told us LOR-253 and Sonidegib may be effective in CRC cancer treatment. Molecular Docking between ATP6V1C2 and 9 first-line and 9 natural drugs showed that ATP6V1C2 was recognized by the best geometrical and energetic matching pattern of 2 First-line and 4 natural drugs. RT-PCR and immunoblotting confirmed that ATP6V1C2 was significantly overexpressed in CRC. Four natural drugs screened by molecular docking were effective in cell proliferation inhibition by CCK8 test. In summary, ATP6V1C2 may be a new therapeutic target for CRC. The illustration is shown in Figure 9., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Developing biomaterials capable of promoting bone regeneration in bacteria-infected sites is of utmost urgency for periodontal disease therapies. Here we produce a hybrid hydrogel by integrating CuS nanoparticles (CuSNPs), which could kill bacteria through photothermal therapy (PTT) triggered by a near infrared (NIR) light, and a gelatin methacryloyl (GelMA) hydrogel, which is injectable and biocompatible. Specifically, CuSNPs were precipitated by chitosan (CS) firstly, then grafted with methacrylic anhydride (MA) to form CuSNP@CS-MA, which was photo-crosslinked with GelMA to synthesize hybrid hydrogels (GelMA/CuSNP). The hybrid hydrogels exhibited a broad-spectrum antibacterial property that could be spatiotemprorally manipulated through applying a NIR light. Their mechanical properties were adjustable by controlling the concentration of CuSNPs, enabling the hydrogels to become more adapted to the oral diseases. Meanwhile, the hybrid hydrogels showed good cytocompatibility in vitro and improved hemostasis in vivo . Moreover, they accelerated alveolar osteogenesis and vascular genesis, successfully treating periodontis in four weeks in a rat model. GelMA/CuSNP hydrogels showed a broad-spectrum sterilization ability via PTT in vitro and outstanding antibacterial property in vivo , suggesting that the hybrid hydrogels could function in the challenging, bacteria-rich, oral environment. Such injectable hybrid hydrogels, capable of achieving both facilitated osteogenesis and NIR-inducible sterilization, represent a new biomaterial for treating periodontitis.

To study the genetic variation leading to the arrest phenotype of pronuclear (PN) zygotes. We recruited a family characterized by recurrent PN arrest during in vitro fertilization (IVF) and intracytoplasmic sperm injection cycles (ICSI) and performed whole-exome sequencing for 2 individuals. The transcriptome profiles of PN-arrest zygotes were assessed by single-cell RNA sequencing analysis. The variants were then validated by PCR amplification and Sanger sequencing in the affected individuals and other family members. A family characterized by recurrent PN arrest during IVF and ICSI cycles were enrolled after giving written informed consent. Peripheral blood samples were taken for DNA extraction. Three PN-arrest zygotes from patient III-3 were used for single-cell RNA-seq as described. This phenotype was reproduced after multiple cycles of egg retrieval and after trying different fertilization methods and multiple ovulation regimens. The mutant genes of whole exon sequencing were screened and verified. The missense variant c. C1630T (p.R544W) in RGS12 was responsible for a phenotype characterized by paternal transmission. RGS12 controls Ca 2+ oscillation, which is required for oocyte activation after fertilization. Single-cell transcriptome profiling of PN-arrest zygotes revealed defective established translation, RNA processing and cell cycle, which explained the failure of complete oocyte activation. Furthermore, we identified proximal genes involved in Ca 2+ oscillation-cytostatic factor-anaphase-promoting complex (Ca 2+ oscillation-CSF-APC) signaling, including upregulated CaMKII , ORAI1, CDC20, and CDH1 and downregulated EMI1 and BUB3 . The findings indicate abnormal spontaneous Ca 2+ oscillations leading to oocytes with prolonged low CSF level and high APC level, which resulted in defective nuclear envelope breakdown and DNA replication. We have identified an RGS12 variant as the potential cause of female infertility characterized by arrest at the PN stage during multiple IVF and ICSI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ma, Zhou, Xie, Chen, Wang and Zhang.)

4-Hydroxy-2,5-dimethyl-3 (2H)-furanone (HDMF) is widely used in the food industry as a spice and flavoring agent with high market demand. In this study, fructose-1,6-bisphosphate aldolase (FBA) and triose phosphate isomerase (TPI) were overexpressed in Zygosaccharomyces rouxii in the form of single and double genes, respectively, via electroporation. High-yield HDMF-engineered yeast strains were constructed by combining the analysis of gene expression levels obtained by real-time fluorescence quantitative PCR technology and HDMF production measured by HPLC. The results showed that there was a significant positive correlation between the production of HDMF and the expression levels of the FBA and TPI genes in yeast; the expression levels of the FBA and TPI genes were also positively correlated ( p  < 0.05). Compared with the wild type (WT), the engineered strains F10-D, T17-D, and TF15-A showed marked increases in HDMF production and FBA and TPI gene expression ( p  < 0.05) and exhibited great genetic stability with no obvious differences in biomass or colony morphology. In addition, the exogenous addition of d-fructose promoted the growth of Z. rouxii . Among the engineered strains, when fermented in YPD media supplemented with d-fructose for 5 days, TF15-A (overexpressing the FBA and TPI genes) generated the highest HDMF production of 13.39 mg/L, which is 1.91 times greater than that of the wild-type strain. The results above indicated that FBA and TPI, which are key enzymes involved in the process of HDMF biosynthesis by Z. rouxii , positively regulate the synthesis of HDMF at the transcriptional level. d-fructose can be used as a precursor for the biosynthesis of HDMF by engineered yeast in industrial production., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Liu, Chen, Li, Hu, Fan, Yan, Liu, Zhou, Jiang, Rui and Dai.)

Ovarian cancer (OC) is a major cause of gynecological cancer mortality, necessitating enhanced research. Organoids, cellular clusters grown in 3D model, have emerged as a disruptive paradigm, transcending the limitations inherent to conventional models by faithfully recapitulating key morphological, histological, and genetic attributes. This review undertakes a comprehensive exploration of the potential in organoids derived from murine, healthy population, and patient origins, encompassing a spectrum that spans foundational principles to pioneering applications. Organoids serve as preclinical models, allowing us to predict how patients will respond to treatments and guiding the development of personalized therapies. In the context of evaluating new drugs, organoids act as versatile platforms, enabling thorough testing of innovative combinations and novel agents. Remarkably, organoids mimic the dynamic nature of OC progression, from its initial formation to the spread to other parts of the body, shedding light on intricate details that hold significant importance. By functioning at an individualized level, organoids uncover the complex mechanisms behind drug resistance, revealing strategic opportunities for effective treatments., (© 2024. The Author(s).)

RNA plays an indispensable role in mammalian cell functions. Cas13, a class of RNA-guided ribonuclease, is a flexible tool for modifying and regulating coding and non-coding RNAs, with enormous potential for creating new cell functions. However, the lack of control over Cas13 activity has limited its cell engineering capability. Here, we present the CRISTAL (Control of RNA with Inducible SpliT CAs13 Orthologs and Exogenous Ligands) platform. CRISTAL is powered by a collection (10 total) of orthogonal split inducible Cas13 effectors that can be turned ON or OFF via small molecules in multiple cell types, providing precise temporal control. Also, we engineer Cas13 logic circuits that can respond to endogenous signaling and exogenous small molecule inputs. Furthermore, the orthogonality, low leakiness, and high dynamic range of our inducible Cas13d and Cas13b enable the design and construction of a robust incoherent feedforward loop, leading to near-perfect and tunable adaptation response. Finally, using our inducible Cas13 effectors, we achieve simultaneous multiplexed control of multiple genes in vitro and in mice. Together, our CRISTAL design represents a powerful platform for precisely regulating RNA dynamics to advance cell engineering and elucidate RNA biology., (© 2024. The Author(s).)

Dry eye (DE) is a multifactorial ocular surface disease characterised by an imbalance in tear homeostasis. The pathogenesis of DE is complex and related to environmental, immunological (e.g., T helper 17 cells) and other factors. However, the DE disease pathogenesis remains unclear, thereby affecting its clinical treatment. This study aimed to explore the mechanism through which prostaglandin E2 (PGE2) affects DE inflammation by regulating Th17. The DE mouse model was established through subcutaneous injection of scopolamine hydrobromide. The tear secretion test and break-up time (BUT) method were used to detect tear secretion and tear film BUT, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of PGE2, interleukin (IL)-17, IL-6 and tumour necrosis factor (TNF-α) in tear fluid and those of PGE2 and IL-17 in the serum. RT-qPCR and western blotting were used to test the mRNA and protein expression levels of IL-17 and retinoid-related orphan receptor-γt (RORγt). PGE2 was highly expressed in the DE mouse model. The mRNA and protein levels of IL-17 and the key Th17 transcription factor RORγt were increased in tissues of the DE mice. Moreover, PGE2 promoted tear secretion, reduced the BUT, increased the IL-17 concentration in tears and increased the Th17 cell proportion in DE, whereas the PGE2 receptor inhibitor AH6809 reversed the effects of PGE2 on tear secretion, BUT, and the Th17 cell proportion in draining lymph node (DLN) cells. Taken together, the study findings indicate that PGE2 could induce DE-related symptoms by promoting Th17 differentiation., (© 2024 John Wiley & Sons Ltd.)

Background: Brain metastases (BM) happen frequently in lung cancer patients and lead to a poor prognosis as well as a lower quality of life. The aim of this study was to identify risk factors for BM in locally advanced non-small cell lung cancer (LA-NSCLC) patients receiving radical radiotherapy, which will be useful for selecting appropriate patient population for further intervention and future trial design., Methods: This was a retrospective cohort study. Patients with inoperable stage IIB-IIIC NSCLC were treated consecutively with definitive thoracic radiotherapy from January 2018 to December 2021, and were retrospectively reviewed and enrolled. Patients with various clinical variables were analyzed to clarify their impact on BM with competing risk models by Fine and Gray., Results: A total of 134 patients were enrolled in this study. The median follow-up for all patients was 37 months [95% confidence interval (CI): 30.5-43.5 months]. BM occurred in 25 patients at the time of analysis. The 1-year and 3-year cumulative BM incidence were 10.5% and 19.9%, respectively. Patients with BM had worse overall survival than those without BM [stratified hazard ratio (HR) for death: 2.83; 95% CI:1.31-6.11; P<0.001]. Based on univariate analyses, non-squamous cell carcinoma (non-SCC), biological effective dose (BED) and planning target volume (PTV) were used as input variables in multivariable analysis (P<0.01). According to multivariate analysis, non-SCC (P<0.001; HR: 6.08; 95% CI: 2.26-16.37), BED <72 Gy (P=0.017; HR: 2.81; 95% CI: 1.20-6.57), and PTV >157.73 cm 3 (P=0.043; HR: 2.56; 95% CI: 1.03-6.35) were independent risk factors for BM. In subgroup analysis of adenocarcinoma with known epidermal growth factor receptor ( EGFR ) mutation status, PTV >157.73 cm 3 and positive EGFR mutation were independent predictors for BM., Conclusions: In this retrospective study, we found that BED <72 Gy and PTV >157.73 cm 3 were significantly associated with BM development and we validated that non-SCC and positive EGFR mutation were risk factors for BM. More research is required to screen the high-risk patient population., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1435/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Creating a perfect catalyst to operate enzyme-like chiral recognition has been a long-sought aim. A challenging example in this context is constructing acyclic all-carbon quaternary stereogenic centers by transition metal-catalyzed enantioselective C-H activation. We now report highly enantioselective iridium-catalyzed primary C-H borylation of α-all-carbon substituted 2,2-dimethyl amides enabled by a tailor-made chiral bidentate boryl ligand ( CBL ). The success of the current transformation is attributed to the CBL /iridium catalyst, which has a confined chiral pocket. This protocol provides a diverse array of acyclic all-carbon quaternary stereocenters with excellent enantiocontrol and distinct structural features. Computational study reveals that steric hindrance of CBL could regulate the type of dominant orbital interaction between the catalyst and substrate, which is crucial to conferring high chiral induction.

Introduction: Prior studies have discussed rapid eye movement (REM) sleep disturbance as a potential endophenotype of major depressive disorder (MDD). However, the neural substrates underlying the percentage of REM sleep duration (REM%) and its association with disease progression in MDD remain unclear., Methods: One hundred and fourteen MDD patients and 74 healthy controls (HCs) underwent resting-state functional and perfusion magnetic resonance imaging (MRI) scans as well as overnight polysomnography examination to assess brain function and REM%, with 48 patients completing follow-up visits. Correlation and mediation analyses were conducted to investigate the associations among baseline REM%, multimodal brain imaging measures, and the improvement of depressive symptoms at follow-up in MDD., Results: We found voxel-wise correlations between baseline REM% and multimodal brain imaging metrics in many brain regions involved in sensorimotor, visual processing, emotion, and cognition in patients with MDD. Moreover, the baseline REM% was correlated with the improvement of depressive symptoms from acute to remitted status in patients through regulating brain activity in the left inferior temporal gyrus and cerebral blood flow in the bilateral paracentral lobule., Conclusion: Our findings help to identify the neural underpinnings of REM% in depression and highlight REM% as a potential prognostic biomarker to predict disease progression. These may inform future novel interventions of MDD from the perspective of regulating REM sleep., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Image sentiment analysis technology can predict, measure and understand the emotional experience of human beings through images. Aiming at the problem of extracting emotional characteristics in art appreciation, this article puts forward an innovative method. Firstly, the PageRank algorithm is enhanced using tweet content similarity and time factors; secondly, the SE-ResNet network design is used to integrate Efficient Channel Attention (ECA) with the residual network structure, and ResNeXt50 is optimized to enhance the extraction of image sentiment features. Finally, the weight coefficients of overall emotions are dynamically adjusted to select a specific emotion incorporation strategy, resulting in effective bimodal fusion. The proposed model demonstrates exceptional performance in predicting sentiment labels, with maximum classification accuracy reaching 88.20%. The accuracy improvement of 21.34% compared to the traditional deep convolutional neural networks (DCNN) model attests to the effectiveness of this study. This research enriches images and texts' emotion feature extraction capabilities and improves the accuracy of emotion fusion classification., Competing Interests: The author has no conflict of interest., (© 2023 Yang and Chen.)

Rapid advances in nanomedicine have enabled potential applications in cancer therapy. The enhanced permeability and retention (EPR) effect is the primary rationale for the passive targeting of nanoparticles in oncology. However, growing evidence indicates that the accumulation of nanomaterials via the EPR effect could be more efficient. Inspired by our clinical observation of the Gap Junction connecpion between folliculostellate cells and pituitary adenoma cells, we designed a novel drug delivery system that targets tumours by coating folliculostellate cell (FS) membranes onto PLGA nanoparticles (NPs). The resulting FSNPs, inheriting membrane proteins from the folliculostellate cell membrane, significantly enhanced the EPR effect compared to nanoparticles without cancer cell membranes. We further demonstrated that mitotane encapsulation improved the therapeutic efficacy of mitotane in both heterotopic and orthotopic pituitary adenoma models. Owing to its significant efficacy, our FS cell membrane-coated nanoplatforms has the potential to be translated into clinical applications for the treatment of invasive pituitary adenoma., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Neoadjuvant immunochemotherapy may benefit patients with non-small cell lung cancer (NSCLC), but its impact requires further investigation., Methods: A meta-analysis was conducted. PubMed, Embase, Web of Science, and the Cochrane Library were searched. The study was registered in PROSPERO (registration no. CRD42022360893)., Results: 60 studies of 3,632 patients were included. Comparing with neoadjuvant chemotherapy, neoadjuvant immunochemotherapy showed higher pCR (RR: 4.71, 95% CI: 3.69, 6.02), MPR (RR, 3.20, 95% CI: 2.75, 3.74), and ORR (RR, 1.46, 95% CI: 1.21, 1.77), fewer surgical complications (RR: 0.67, 95%CI: 0.48, 0.94), higher R0 resection rate (RR: 1.06, 95%CI: 1.03, 1.10, I 2  = 52%), and longer 1-year and 2-year OS, without affecting TRAEs. For neoadjuvant immunochemotherapy in NSCLC, the pooled pCR rate was 0.35 (95% CI: 0.31, 0.39), MPR was 0.59 (95% CI: 0.54, 0.63), and ORR was 0.71 (95% CI: 0.66, 0.76). The pooled incidence of all grade TRAEs was 0.70 (95% CI: 0.60, 0.81), and that of >= grade 3 TRAEs was 0.24 (95% CI: 0.16, 0.32). The surgical complications rate was 0.13 (95% CI: 0.07, 0.18) and R0 resection rate was 0.98 (95% CI: 0.96, 0.99). The pooled 1-year OS was 0.97 (95%CI: 0.96, 0.99), and 2-year OS was 0.89 (95%CI: 0.83, 0.94). Patients with squamous cell carcinoma, stage III or higher PD-L1 performed better. Notably, no significant differences were observed in pCR, MPR, and ORR between 2 or more treatment cycles. Pembrolizumab-, or toripalimab-based neoadjuvant immunochemotherapy demonstrated superior efficacy and tolerable toxicity., Conclusion: According to our analysis, reliable efficacy, safety, and survival of neoadjuvant immunochemotherapy for operable NSCLC were demonstrated., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42022360893, identifier CRD42022360893., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zheng, Feng, Chen and You.)

The important parameters affecting the nutritional properties of lipids were analyzed and compared between human milk (HM), infant formulas (IFs), mammalian milk, and substitute fat, including molecular species, fatty acid composition, glyceride content, and important structural triacylglycerols (TAGs). The molecular species of triacylglycerols with functional fatty acids were significantly different between HM and IFs, and their contents in HM were significantly higher than those in IFs. Accordingly, the evaluation scores of fatty acid composition and glyceride content in IFs were less than 50 compared to HM. Although the introduction of vegetable oils effectively improved the unsaturation of IF lipid, the excessive addition of TAGs rich in oleic and linoleic acid resulted in an imbalance of TAG composition and structure. Only 36.84 % of IFs were supplemented with structured lipids, but those still lacked sn -2 palmitate TAGs. The adoption of multiple lipids and novel processing technologies is required for novel IFs to match the composition, content, positional structure and spherical membrane structure of HM as closely as possible., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Introduction: Gastric cancer (GC) is the fifth most prevalent cancer globally, with the third highest case fatality rate. Neutrophil extracellular traps (NETs) are a reticulated structure of DNA, histones, and antimicrobial peptides produced by active neutrophils that trap pathogens. Even though NETs are associated with poorer recurrence-free survival (RFS) and overall survival (OS), the specifics of this interaction between NETs and cancer cells are yet unknown., Methods: The keywords "neutrophil extracellular traps and gastric cancer" were used in the GEO database for retrieval, and the GSE188741 dataset was selected to obtain the NETs-related gene. 27 NETs-related genes were screened by univariate Cox regression analysis ( p < 0.05). 27 NETs-related genes were employed to identify and categorize NETs-subgroups of GC patients under the Consensus clustering analysis. 808 GC patients in TCGA-STAD combined with GES84437 were randomly divided into a training group ( n = 403) and a test group ( n = 403) at a ratio of 1:1 to validate the NETs-related signature., Results: Based on Multivariate Cox regression and LASSO regression analysis to develop a NETs-related prognosis model. We developed a very specific nomogram to improve the NETs-clinical score's usefulness. Similarly, we also performed a great result in pan-cancer study with NETs-score. Low NETs scores were linked to higher MSI-H (microsatellite instability-high), mutation load, and immune activity. The cancer stem cell (CSC) index and chemotherapeutic treatment sensitivity were also connected to the NET score. Our comprehensive analysis of NETs in GC suggests that NETs have a role in the tumor microenvironment, clinicopathological features, and prognosis., Discussion: The NETs-score risk model provides a basis for better prognosis and therapy outcomes in GC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Zhao, Mak, Wang, Chen, Ren, Yu and Zhang.)

Characterized by nucleus pulposus (NP) cell senescence and extracellular matrix (ECM) degradation, disc degeneration is a common pathology for various degenerative spinal disorders. To date, effective treatments for disc degeneration are absent. Here, we found that Glutaredoxin3 (GLRX3) is an important redox-regulating molecule associated with NP cell senescence and disc degeneration. Using a hypoxic preconditioning method, we developed GLRX3 + mesenchymal stem cell-derived extracellular vehicles (EVs-GLRX3), which enhanced the cellular antioxidant defense, thus preventing reactive oxygen species (ROS) accumulation and senescence cascade expansion in vitro . Further, a disc tissue-like biopolymer-based supramolecular hydrogel, which was injectable, degradable, and ROS-responsive, was proposed to deliver EVs-GLRX3 for treating disc degeneration. Using a rat model of disc degeneration, we demonstrated that the EVs-GLRX3-loaded hydrogel attenuated mitochondrial damage, alleviated the NP senescence state, and restored ECM deposition by modulating the redox homeostasis. Our findings suggested that modulation of redox homeostasis in the disc can rejuvenate NP cell senescence and thus attenuate disc degeneration.

Sarcopenia and osteoporosis, two degenerative diseases in older patients, have become severe health problems in aging societies. Muscles and bones, the most important components of the motor system, are derived from mesodermal and ectodermal mesenchymal stem cells. The adjacent anatomical relationship between them provides the basic conditions for mechanical and chemical signals, which may contribute to the co-occurrence of sarcopenia and osteoporosis. Identifying the potential common crosstalk genes between them may provide new insights for preventing and treating their development. In this study, DEG analysis, WGCNA, and machine learning algorithms were used to identify the key crosstalk genes of sarcopenia and osteoporosis; this was then validated using independent datasets and clinical samples. Finally, four crosstalk genes ( ARHGEF10 , PCDH7 , CST6 , and ROBO3 ) were identified, and mRNA expression and protein levels of PCDH7 in clinical samples from patients with sarcopenia, with osteoporosis, and with both sarcopenia and osteoporosis were found to be significantly higher than those from patients without sarcopenia or osteoporosis. PCDH7 seems to be a key gene related to the development of both sarcopenia and osteoporosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Wang, Shi, Yang, Wang, Chen, Li, Chen and Sun.)

Background: Gastric cancer (GC) is one of the most common malignancies in the human digestive tract. CD4+T cells can eliminate tumor cells directly through the mechanism of cytolysis, they can also indirectly attack tumor cells by regulating the tumor TME. A prognostic model of CD4+T cells is urgently needed to improve treatment strategies and explore the specifics of this interaction between CD4+T cells and gastric cancer cells. Methods: The detailed data of GC samples were downloaded from the Cancer Genome Atlas (TCGA), GSE66229, and GSE84437 datasets. CD4 + T cell-related genes were identified to construct a risk-score model by using the Cox regression method and validated with the Gene Expression Omnibus (GEO) dataset. In addition, postoperative pathological tissues of 139 gastric cancer patients were randomly selected for immunohistochemical staining, and their prognostic information were collected for external verification. Immune and molecular characteristics of these samples and their predictive efficacy in immunotherapy and chemotherapy were analysed. Results: The training set and validation set had consistent results, with GC patients of high PROC and SERPINE1 expression having poorer prognosis. In order to improve their clinical application value, we constructed a risk scoring model and established a high-precision nomogram. Low-risk patients had a better overall survival (OS) than high-risk patients, consistent with the results from the GEO cohort. Furthermore, the risk-score model can predict infiltration of immune cells in the tumor microenvironment of GC, as well as the response of immunotherapy. Correlations between the abundance of immune cells with PROC and SERPINE1 genes were shown in the prognostic model according to the training cohort. Finally, sensitive drugs were identified for patients in different risk subgroup. Conclusion: The risk model not only provides a basis for better prognosis in GC patients, but also is a potential prognostic indicator to distinguish the molecular and immune characteristics of the tumor, and its response to immune checkpoint inhibitor (ICI) therapy and chemotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Li, Mak, Wang, Ren, Wang, Kuo, Wu, Li, Hao, Zhang and He.)

Background: Previous studies have shown that systemic inflammation indicators could predict the survival outcomes of patients with malignant tumors receiving various treatments. Radiotherapy, as a crucial treatment modality, effectively alleviates discomfort in patients with bone metastasis (BM) and greatly improves the quality of life for them. This study aimed to investigate the prognostic value of systemic inflammation index in hepatocellular carcinoma (HCC) patients with BM treated with radiotherapy., Methods: We retrospectively analyzed clinical data collected from HCC patients with BM who received radiotherapy in our institution between January 2017 and December 2021. The pre-treatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were derived to determine their relationship with overall survival (OS) and progression-free survival (PFS), using the Kaplan-Meier survival curves. The optimal cut-off value of the systemic inflammation indicators for predicting prognosis was assessed by receiver operating characteristic (ROC) curves. Univariate and multivariate analyses were performed to ultimately evaluate the factors associated with survival., Results: The study included 239 patients with a median 14-month follow-up. The median OS was 18 months (95% confidence interval [CI] = 12.0-24.0) and the median PFS was 8.5 months (95% CI = 6.5-9.5). The optimal cut-off values for the patients were determined by ROC curve analysis as follows: SII =395.05, NLR=5.43 and PLR = 108.23. The area under the receiver operating characteristic curve values for SII, NLR and PLR in disease control prediction were 0.750, 0.665 and 0.676, respectively. Elevated systemic immune-inflammation index (SII>395.05) and higher NLR (NLR>5.43) were independently associated with poor OS and PFS. In multivariate analysis, Child-Pugh class (P = 0.038), intrahepatic tumor controlled (P = 0.019), SII (P = 0.001) and NLR (P = 0.007) were independent prognostic factors of OS and Child-Pugh class (P = 0.042), SII (P < 0.001) and NLR (P = 0.002) were independently correlated with PFS., Conclusion: NLR and SII were associated with poor prognosis in HCC patients with BM receiving radiotherapy and might be considered reliable and independent prognostic biomarkers for HCC patients with BM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Huang, Xu, Fan, Zhang, Li, Zeng and He.)

Background: Stereotactic body radio therapy (SBRT) has emerged as a standard treatment option for nonsurgical candidates with early-stage non-small cell lung cancer (NSCLC). Pathological proof is sometimes difficult to obtain in patients with solitary pulmonary nodules (SPNs). We aimed to compare the clinical outcomes of stereotactic body radiotherapy via helical tomotherapy (HT-SBRT) for early-stage lung cancer patients with or without a pathological diagnosis., Methods: Between June 2011 and December 2016, we treated 119 lung cancer patients with HT-SBRT, including 55 with a clinical diagnosis and 64 with a pathological diagnosis. Survival outcomes, including local control (LC), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS), were compared between two cohorts with and without a pathological diagnosis., Results: The median follow-up for the whole group was 69 months. Patients with a clinical diagnosis were significantly older (p = 0.002). No significant differences were observed between the clinical and pathological diagnosis cohorts in terms of the long-term outcome, with 5-year LC, PFS, CSS, and OS of 87% versus 83% (p = 0.58), 48% versus 45% (p = 0.82), 87% versus 84% (p = 0.65), and 60% versus 63% (p = 0.79), respectively. Recurrence patterns and toxicity were also similar., Conclusions: Empiric SBRT appears to be a safe and effective treatment option in a multidisciplinary setting when patients with SPNs highly suggestive of malignancy are unable/refuse to obtain a definitive pathological diagnosis., (© 2023. The Author(s).)