Ubiquitin-induced RNF168 condensation promotes DNA double-strand break repair.

Rapid accumulation of repair factors at DNA double-strand breaks (DSBs) is essential for DSB repair. Several factors involved in DSB repair have been found undergoing liquid-liquid phase separation (LLPS) at DSB sites to facilitate DNA repair. RNF168, a RING-type E3 ubiquitin ligase, catalyzes H2A.X ubiquitination for recruiting DNA repair factors. Yet, whether RNF168 undergoes LLPS at DSB sites remains unclear. Here, we identified K63-linked polyubiquitin-triggered RNF168 condensation which further promoted RNF168-mediated DSB repair. RNF168 formed liquid-like condensates upon irradiation in the nucleus while purified RNF168 protein also condensed in vitro. An intrinsically disordered region containing amino acids 460-550 was identified as the essential domain for RNF168 condensation. Interestingly, LLPS of RNF168 was significantly enhanced by K63-linked polyubiquitin chains, and LLPS largely enhanced the RNF168-mediated H2A.X ubiquitination, suggesting a positive feedback loop to facilitate RNF168 rapid accumulation and its catalytic activity. Functionally, LLPS deficiency of RNF168 resulted in delayed recruitment of 53BP1 and BRCA1 and subsequent impairment in DSB repair. Taken together, our finding demonstrates the pivotal effect of LLPS in RNF168-mediated DSB repair.

Melamine Polymerization Promotes Compact Phosphorus/Carbon Composite for High-Performance and Safe Lithium Storage.

Phosphorus is regarded as a promising material for high-performance lithium-ion batteries (LIBs) due to its high theoretical capacity, appropriate lithiation potential, and low lithium-ion diffusion barrier. Phosphorus/carbon composites (PC) are engineered to serve as high-capacity high-rate anodes; the interaction between phosphorus and carbon, long-term capacity retention, and safety problems are important issues that must be well addressed simultaneously. Herein, an in situ polymerization approach to fabricate a poly-melamine-hybridized (pMA) phosphorus/carbon composite (pMA-PC) is employed. The pMA hybridization enhances the density and electrical conductivity of the PC, improves the structural integrity, and facilitates stable electron transfer within the pMA-PC composite. Moreover, the pMA-PC composite exhibits efficient adsorption of lithium polysulfides, enabling stable transport of Li+ ions. Therefore, the pMA-PC anode demonstrates a high specific charging capacity of 1,381 mAh g-1 at 10 A g-1, and a great capacity retention of 86.7% at 1 A g-1 over 500 cycles. The synergistic effect of phosphorus and nitrogen further confers excellent flame retardant properties to the pMA-PC anode, including self-extinguishing in 2.5 s, and a much lower combustion temperature than PC. The enhanced capacity and safety performance of pMA-PC show potential in future high-capacity and high-rate LIBs.

Immune infiltration is associated with pan-cancer prognostic biomarker RING finger protein 187.

Cancer is associated with the highest mortality rate globally. While life-saving screening and treatments exist, better awareness is needed. RNF187, an E3 ligase regulating biological processes, belongs to the RING domain-containing E3 ligase family. RNF187 may serve as an oncogene due to abnormal expression in tumors. However, its association with immune infiltration and prognosis across various cancers remains unclear. We searched several databases including TCGA, GTE x, CCLE, TIMER, and GSEA. R software was used to evaluate RNF187 differential expression, survival, pathology stage, DNA methylation, tumor mutational burden (TMB), microsatellite instability (MSI), gene co-expression analysis, mismatch repairs (MMRs), tumor microenvironment (TME), and immune cell infiltration. Clinicopathological data were collected, and immunohistochemistry was used to verify RNF187 expression in tumor tissues. RNF187 expression was up-regulated in various cancers compared to that in normal tissues and associated with poor patient outcomes. Dysregulation of RNF187 expression in multiple cancer types was strongly correlated with DNA methylation, MMR, MSI, and TMB. RNF187 could interact with different immune cells in cancers. Biomarkers associated with RNF187 may be helpful for prognosis and immunology in treating pan-cancer patients.

The RNA-binding protein sorbin and SH3 domain-containing 2 are transcriptionally regulated by specificity protein 1 and function as tumor suppressors in bladder cancer by stabilizing tissue factor pathway inhibitor.

Sorbin and SH3 domain-containing 2 (SORBS2) is an RNA-binding protein and has been implicated in the development of some cancers. However, its role in bladder cancer (BC) is yet to be established. The expression of SORBS2 in BC tissues was determined from the Gene Expression Omnibus and Gene Expression Profiling Interactive Analysis databases and collected paired tumor/normal samples. The effects of SORBS2 on BC cells were detected by CCK-8, colony formation, Transwell, dual-luciferase, RNA immunoprecipitation, chromatin immunoprecipitation, and DNA pull-down assays. In vivo, BC cell growth and metastasis were studied by a xenograft subcutaneous model and a tail-vein metastasis model. The results showed that SORBS2 expression was significantly decreased in BC tissues and cells. SORBS2 overexpression inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro and tumor growth and metastasis in vivo, while silencing SORBS2 produced the opposite effect. Mechanistically, we found that SORBS2 enhanced the stability of tissue factor pathway inhibitor (TFPI) mRNA via direct binding to its 3' UTR. Restoration of TFPI expression reversed SORBS2 knockdown-induced malignant phenotypes of BC cells. In addition, SORBS2 expression was negatively regulated by the transcription factor specificity protein 1 (SP1). Conversely, SORBS2 can be transcriptionally regulated by SP1 and inhibit BC cell growth and metastasis via stabilization of TFPI mRNA, indicating SORBS2 may be a promising therapeutic target for BC.

Chemical and Structural Engineering of Gelatin-Based Delivery Systems for Therapeutic Applications: A Review.

As a biodegradable and biocompatible protein derived from collagen, gelatin has been extensively exploited as a fundamental component of biological scaffolds and drug delivery systems for precise medicine. The easily engineered gelatin holds great promise in formulating various delivery systems to protect and enhance the efficacy of drugs for improving the safety and effectiveness of numerous pharmaceuticals. The remarkable biocompatibility and adjustable mechanical properties of gelatin permit the construction of active 3D scaffolds to accelerate the regeneration of injured tissues and organs. In this Review, we delve into diverse strategies for fabricating and functionalizing gelatin-based structures, which are applicable to gene and drug delivery as well as tissue engineering. We emphasized the advantages of various gelatin derivatives, including methacryloyl gelatin, polyethylene glycol-modified gelatin, thiolated gelatin, and alendronate-modified gelatin. These derivatives exhibit excellent physicochemical and biological properties, allowing the fabrication of tailor-made structures for biomedical applications. Additionally, we explored the latest developments in the modulation of their physicochemical properties by combining additive materials and manufacturing platforms, outlining the design of multifunctional gelatin-based micro-, nano-, and macrostructures. While discussing the current limitations, we also addressed the challenges that need to be overcome for clinical translation, including high manufacturing costs, limited application scenarios, and potential immunogenicity. This Review provides insight into how the structural and chemical engineering of gelatin can be leveraged to pave the way for significant advancements in biomedical applications and the improvement of patient outcomes.

Palladium-Catalyzed Annulative π-Extension of Bay-Iodinated Triphenylenes to Access Polycyclic Aromatic Compounds.

A palladium-catalyzed annulative π-extension reaction of bay-iodinated triphenylenes with aryl iodides/o-chloroaromatic carboxylic acids was developed. This approach enabled the synthesis of diverse polycyclic aromatic compounds, including dibenzo[fg,op]tetracenes, azadibenzo[fg,op]tetracenes, and tribenzo[a,g,m]coronenes. Initial studies indicate that the resulting product, 2,3,8,9,14,15-hexakis(decyloxy)tribenzo[a,g,m]coronene, exhibits good liquid-crystalline properties.

Pentanary Oxythiogermanates Ba3MGe3O2S8 (M = Ca, Zn) Featuring [Ge3O2S8]8- Trimers and {[MGe3O2S8]6-}∞ Chains: Structural Chemistry and Physical Properties.

Oxychalcogenides are increasingly attracting wide attention because they contain multiple anions that may combine the advantages of oxides and chalcogenides. In this work, two new pentanary oxythiogermanates, Ba3MGe3O2S8 [M = Ca (1), Zn (2)], were synthesized by a high-temperature solid-state reaction. They crystallize in the orthorhombic space group Pnma, and their structures contain isolated [Ge3O2S8]8- units constructed by one [GeO2S2] and two [GeOS3] tetrahedra that link with M2+ ions to build the {[MGe3O2S8]6-}∞ chain, representing a new type of oxythiogermanate. Notably, a [ZnS5] square pyramid exists in 2. Their structural chemistry and relationship with relevant structures are analyzed. 1 and 2 exhibit wide band gaps of 3.93 and 2.63 eV, birefringences of 0.100 and 0.089 at 2100 nm, respectively, and also obvious photocurrent responses. This work may be extended to a family of AE3MIIMIV3O2Q8 (AE = alkali-earth metal; MII = Ca, Zn, Cd, Hg; MIV = Si, Ge, Sn; Q = S, Se), and further systematic survey on them can be performed to enrich the study of multifunctional oxychalcogenides.

Molecular engineering of PETase for efficient PET biodegradation.

The widespread utilization of polyethylene terephthalate (PET) has caused a variety of environmental and health problems. Compared with traditional thermomechanical or chemical PET cycling, the biodegradation of PET may offer a more feasible solution. Though the PETase from Ideonalla sakaiensis (IsPETase) displays interesting PET degrading performance under mild conditions; the relatively low thermal stability of IsPETase limits its practical application. In this study, enzyme-catalysed PET degradation was investigated with the promising IsPETase mutant HotPETase (HP). On this basis, a carbohydrate-binding module from Bacillus anthracis (BaCBM) was fused to the C-terminus of HP to construct the PETase mutant (HLCB) for increased PET degradation. Furthermore, to effectively improve PET accessibility and PET-degrading activity, the truncated outer membrane hybrid protein (FadL) was used to expose PETase and BaCBM on the surface of E. coli (BL21with) to develop regenerable whole-cell biocatalysts (D-HLCB). Results showed that, among the tested small-molecular weight ester compounds (p-nitrophenyl phosphate (pNPP), p-Nitrophenyl acetate (pNPA), 4-Nitrophenyl butyrate (pNPB)), PETase displayed the highest hydrolysing activity against pNPP. HP displayed the highest catalytic activity (1.94 µM(p-NP)/min) at 50 °C and increased longevity at 40 °C. The fused BaCBM could clearly improve the catalytic performance of PETase by increasing the optimal reaction temperature and improving the thermostability. When HLCB was used for PET degradation, the yield of monomeric products (255.7 µM) was ∼25.5 % greater than that obtained after 50 h of HP-catalysed PET degradation. Moreover, the highest yield of monomeric products from the D-HLCB-mediated system reached 1.03 mM. The whole-cell catalyst D-HLCB displayed good reusability and stability and could maintain more than 54.6 % of its initial activity for nine cycles. Finally, molecular docking simulations were utilized to investigate the binding mechanism and the reaction mechanism of HLCB, which may provide theoretical evidence to further increase the PET-degrading activities of PETases through rational design. The proposed strategy and developed variants show potential for achieving complete biodegradation of PET under mild conditions.

Unveiling hormone-stimulated gene mechanisms in prostate cancer: A prognostic model, immune infiltration analysis, and drug sensitivity study.

Hormones promote the progression of prostate cancer (PRCA) through the activation of a complex regulatory network. Inhibition of hormones or modulation of specific network nodes alone is insufficient to suppress the entire oncogenic network. Therefore, it is imperative to elucidate the mechanisms underlying the occurrence and development of PRCA in order to identify reliable diagnostic markers and therapeutic targets. To this end, we used publicly available data to analyze the potential mechanisms of hormone-stimulated genes in PRCA, construct a prognostic model, and assess immune infiltration and drug sensitivity. The single-cell RNA-sequencing data of PRCA were subjected to dimensionality reduction clustering and annotation, and the cells were categorized into two groups based on hormone stimulus-related scores. The differentially expressed genes between the two groups were screened and incorporated into the least absolute shrinkage and selection operator machine learning algorithm, and a prognostic model comprising six genes (ZNF862, YIF1A, USP22, TAF7, SRSF3, and SPARC) was constructed. The robustness of the model was validation through multiple methods. Immune infiltration scores in the two risk groups were calculated using three different algorithms. In addition, the relationship between the model genes and immune cell infiltration, and that between risk score and immune cell infiltration were analyzed. Drug sensitivity analysis was performed for the model genes and risk score using public databases to identify potential candidate drugs. Our findings provide novel insights into the mechanisms of hormone-stimulated genes in PRCA progression, prognosis, and drug screening.

A 4D-Printable Photocurable Resin Derived from Waste Cooking Oil with Enhanced Tensile Strength.

In pursuit of enhancing the mechanical properties, especially the tensile strength, of 4D-printable consumables derived from waste cooking oil (WCO), we initiated the production of acrylate-modified WCO, which encompasses epoxy waste oil methacrylate (EWOMA) and epoxy waste oil acrylate (EWOA). Subsequently, a series of WCO-based 4D-printable photocurable resins were obtained by introducing a suitable diacrylate molecule as the second monomer, coupled with a composite photoinitiator system comprising Irgacure 819 and p-dimethylaminobenzaldehyde (DMAB). These materials were amenable to molding using an LCD light-curing 3D printer. Our findings underscored the pivotal role of triethylene glycol dimethacrylate (TEGDMA) among the array of diacrylate molecules in enhancing the mechanical properties of WCO-based 4D-printable resins. Notably, the 4D-printable material, composed of EWOA and TEGDMA in an equal mass ratio, exhibited nice mechanical strength comparable to that of mainstream petroleum-based 4D-printable materials, boasting a tensile strength of 9.17 MPa and an elongation at break of 15.39%. These figures significantly outperformed the mechanical characteristics of pure EWOA or TEGDMA resins. Furthermore, the EWOA-TEGDMA resin demonstrated impressive thermally induced shape memory performance, enabling deformation and recovery at room temperature and retaining its shape at -60 °C. This resin also demonstrated favorable biodegradability, with an 8.34% weight loss after 45 days of soil degradation. As a result, this 4D-printable photocurable resin derived from WCO holds immense potential for the creation of a wide spectrum of high-performance intelligent devices, brackets, mold, folding structures, and personalized products.

[Analysis of a child with DIGFAN syndrome due to variant of MORC2 gene].

OBJECTIVE: To explore the clinical features and genetic etiology for a child with developmental delay, impaired growth, facial dysmorphism, and axonal neuropathy (DIGFAN). METHODS: A child who was admitted to the Second Affiliated Hospital of Guangxi Medical University on March 22, 2021 was selected the study subject. Clinical data of the child was collected. Following extraction of genomic DNA, the child and his parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 10-year-and-9-month-old boy, had manifested with short stature, intellectual disability, delayed speech, motor and language development, and facial dysmorphism. WES and Sanger sequencing revealed that he has harbored a novel de novo c.800T>C (p.Leu267Pro) variant of the MORC2 gene. The Leucine at position 267, which is highly conserved among various species, is located in the S5 domain of ribosome protein in the ATPase binding region of MORC2. And the Leu267Pro may affect the function of MORC2 by altering the spatial conformation and activity of ATPase. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.800T>C variant was classified as likely pathogenic (PS2+PM2_Supporting+PP2+PP3). CONCLUSION: The MORC2: c.800T>C (p.Leu267Pro) variant probably underlay the pathogenesis of DIGFAN syndrome in this child.

In-Situ Cyclized Polyacrylonitrile as an Electron Selective Layer for n-i-p Perovskite Solar Cell with Enhanced Efficiency and Stability.

In situ cyclized polyacrylonitrile (CPAN) is developed to replace n-type metal oxide semiconductors (TiO2 or SnO2) as an electron selective layer (ESL) for highly efficient and stable n-i-p perovskite solar cells (PSCs). The CPAN layer is fabricated via facile in situ cyclization reaction of polyacrylonitrile (PAN) coated on a conducting glass substrate. The CPAN layer is robust and insoluble in common solvents, and possesses n-type semiconductor properties with a high electron mobility of 4.13×10-3 cm2 V-1 s-1. With the CPAN as an ESL, the PSC affords a power conversion efficiency (PCE) of 23.12 %, which is the highest for the n-i-p PSCs with organic ESLs. Moreover, the device with the CPAN layer holds superior operational stability, maintaining over 90 % of their initial efficiency after 500 h continuous light soaking. These results confirm that the CPAN layer would be a desirable low-cost and efficient ESL for n-i-p PSCs and other photoelectronic devices with high performance and stability.

Monolithic Interphase Enables Fast Kinetics for High-Performance Sodium-Ion Batteries at Subzero Temperature.

In spite of the competitive performance at room temperature, the development of sodium-ion batteries (SIBs) is still hindered by sluggish electrochemical reaction kinetics and unstable electrode/electrolyte interphase under subzero environments. Herein, a low-concentration electrolyte, consisting of 0.5M NaPF6 dissolving in diethylene glycol dimethyl ether solvent, is proposed for SIBs working at low temperature. Such an electrolyte generates a thin, amorphous, and homogeneous cathode/electrolyte interphase at low temperature. The interphase is monolithic and rich in organic components, reducing the limitation of Na+ migration through inorganic crystals, thereby facilitating the interfacial Na+ dynamics at low temperature. Furthermore, it effectively blocks the unfavorable side reactions between active materials and electrolytes, improving the structural stability. Consequently, Na0.7Li0.03Mg0.03Ni0.27Mn0.6Ti0.07O2//Na and hard carbon//Na cells deliver a high capacity retention of 90.8 % after 900 cycles at 1C, a capacity over 310 mAh g-1 under -30 °C, respectively, showing long-term cycling stability and great rate capability at low temperature.

[Effect and mechanism of Jiming Powder on myocardial fibrosis in mice with myocardial infarction].

Jiming Powder is a traditional ancient prescription with good therapeutic effect in the treatment of heart failure, but its mechanism lacks further exploration. In this study, a mouse model of coronary artery ligation was used to evaluate the effect and mechanism of Jiming Powder on myocardial fibrosis in mice with myocardial infarction. The study constructed a mouse model of heart failure after myocardial infarction using the method of left anterior descending coronary artery ligation. The efficacy of Jiming Powder was evaluated from multiple angles, including ultrasound imaging, hematoxylin-eosin(HE) staining, Masson staining, Sirius Red staining, and serum myocardial enzyme spectrum detection. Western blot analysis was performed to detect key proteins involved in ventricular remodeling, including transforming growth factor-ß1(TGF-ß1), α-smooth muscle actin(α-SMA), wingless-type MMTV integration site family member 3a(Wnt3a), ß-catenin, matrix metallopeptidase 2(MMP2), matrix metallopeptidase 3(MMP3), TIMP metallopeptidase inhibitor 1(TIMP1), and TIMP metallopeptidase inhibitor 2(TIMP2). The results showed that compared with the model group, the high and low-dose Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVID;s) and diastole(LVID;d), increased the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improved cardiac function in mice after myocardial infarction, and effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactic dehydrogenase(LDH), thus protecting ischemic myocardium. HE staining showed that Jiming Powder could attenuate myocardial inflammatory cell infiltration after myocardial infarction. Masson and Sirius Red staining demonstrated that Jiming Powder effectively inhibited myocardial fibrosis, reduced the collagen Ⅰ/Ⅲ ratio in myocardial tissues, and improved collagen remodeling after myocardial infarction. Western blot results showed that Jiming Powder reduced the expression of TGF-ß1, α-SMA, Wnt3a, and ß-catenin, decreased the levels of MMP2, MMP3, and TIMP2, and increased the level of TIMP1, suggesting its role in inhibiting cardiac fibroblast transformation, reducing extracellular matrix metabolism in myocardial cells, and lowering collagen Ⅰ and α-SMA content, thus exerting an anti-myocardial fibrosis effect after myocardial infarction. This study revealed the role of Jiming Powder in improving ventricular remodeling and treating myocardial infarction, laying the foundation for further research on the pharmacological effect of Jiming Powder.

Automated identification and segmentation of urine spots based on deep-learning.

Micturition serves an essential physiological function that allows the body to eliminate metabolic wastes and maintain water-electrolyte balance. The urine spot assay (VSA), as a simple and economical assay, has been widely used in the study of micturition behavior in rodents. However, the traditional VSA method relies on manual judgment, introduces subjective errors, faces difficulty in obtaining appearance time of each urine spot, and struggles with quantitative analysis of overlapping spots. To address these challenges, we developed a deep learning-based approach for the automatic identification and segmentation of urine spots. Our system employs a target detection network to efficiently detect each urine spot and utilizes an instance segmentation network to achieve precise segmentation of overlapping urine spots. Compared with the traditional VSA method, our system achieves automated detection of urine spot area of micturition in rodents, greatly reducing subjective errors. It accurately determines the urination time of each spot and effectively quantifies the overlapping spots. This study enables high-throughput and precise urine spot detection, providing important technical support for the analysis of urination behavior and the study of the neural mechanism underlying urination.

Learning With Constraint Learning: New Perspective, Solution Strategy and Various Applications.

The complexity of learning problems, such as Generative Adversarial Network (GAN) and its variants, multi-task and meta-learning, hyper-parameter learning, and a variety of real-world vision applications, demands a deeper understanding of their underlying coupling mechanisms. Existing approaches often address these problems in isolation, lacking a unified perspective that can reveal commonalities and enable effective solutions. Therefore, in this work, we proposed a new framework, named Learning with Constraint Learning (LwCL), that can holistically examine challenges and provide a unified methodology to tackle all the above-mentioned complex learning and vision problems. Specifically, LwCL is designed as a general hierarchical optimization model that captures the essence of these diverse learning and vision problems. Furthermore, we develop a gradient-response based fast solution strategy to overcome optimization challenges of the LwCL framework. Our proposed framework efficiently addresses a wide range of applications in learning and vision, encompassing three categories and nine different problem types. Extensive experiments on synthetic tasks and real-world applications verify the effectiveness of our approach. The LwCL framework offers a comprehensive solution for tackling complex machine learning and computer vision problems, bridging the gap between theory and practice.

Advanced ethylene-absorbing and cushioning depending on the 3D porous-structured fruit packaging: Toward polyurethane foam manipulation using zein and soybean oil polyol substrates.

Fruits are essential sources of nutrients in our daily diet; however, their spoilage is often intensified by mechanical damage and the ethylene phytohormone, resulting in significant economic losses and exacerbating hunger issues. To address these challenges, this study presented a straightforward in situ synthesis protocol for producing Z/SOPPU foam, a 3D porous-structured fruit packaging. This innovative packaging material offered advanced ethylene-adsorbing and cushioning capabilities achieved through stirring, heating, and standing treatments. The results demonstrated that the Z/SOPPU foam, with its porous structure, served as an excellent packaging material for fruits, maintaining the intact appearance of tomatoes even after being thrown 72 times from a height of 1.5 m. Additionally, it exhibited desirable hydrophobicity (contact angle of 114.31 ± 0.82°), degradability (2.73 ± 0.88 % per 4 weeks), and efficient ethylene adsorption (adsorption rate of 13.2 ± 1.7 mg/m3/h). These remarkable characteristics could be attributed to the unique 3D micron-porous configuration, consisting of soybean oil polyol polyurethane foam for mechanical strain cushioning and zein for enhanced ethylene adsorption efficiency. Overall, this research offers an effective and original approach to the rational design and fabrication of advanced bio-based fruit packaging.

Clinical, Imaging, and Pathological-Molecular Characteristics Associated with Stage IA Invasive Lung Adenocarcinoma Recurrence After Sub-lobar Resection.

RATIONALE AND OBJECTIVES: This study aimed to investigate the association of clinical, imaging, and pathological-molecular characteristics with the prediction of patient prognosis with stage IA invasive lung adenocarcinoma (ILADC) after sub-lobar resection. MATERIALS AND METHODS: This study assessed 360 patients, including 91 and 269 with and without recurrence 3 years postoperatively, respectively, with stage IA ILADC undergoing preoperative chest computed tomography (CT) scans and subsequent sub-lobar resection at our institution. Their clinical and CT features and histological subtypes and gene mutation status were compared. Binary logistic regression analysis was conducted to identify the independent risk factors for recurrence. An external validation cohort included 113 patients, used to test the model's efficiency. RESULTS: For clinical features, old age, male gender, smokers, and high age-adjusted Charlson comorbidity index (ACCI) were frequently observed in patients with recurrence than those without (all p < 0.05). For CT features, large tumor size, solid-predominant density, spiculation, peripheral fibrosis, type II pleural tag, and pleural adhesion were more common in recurrent patients than non-recurrent ones (all p < 0.05). The regression model revealed old age, large tumor size, solid-predominant density, spiculation, type II pleural tag, and pleural adhesion as independent risk factors for recurrence, with an area under the curve (AUC) of 0.942. The external validation cohort obtained an AUC of 0.958. For phological-molecular features, micropapillary/solid-predominant growth pattern, KRAS, ALK, and NRAS mutation or fusion were more common in the recurrent group, whereas EGFR mutation was more frequent in the non-recurrent group (all p < 0.05). CONCLUSION: Clinical and CT features help predict the prognosis of patients with stage IA ILADC after sub-lobar resection and decide for individualized treatment. Moreover, patients with different prognosis demonstrated different pathological-molecular features.

Effects of the enhanced recovery after surgery (ERAS) protocol on the postoperative stress state and short-term complications in elderly patients with colorectal cancer.

OBJECTIVE: The aim of this study was to evaluate the feasibility and necessity of enhanced recovery after surgery in elderly patients with colorectal cancer by observing inflammatory markers and postoperative complications. METHODS: Hospitalized colorectal cancer patients from the Affiliated Hospital of Jiangsu University from January 2021 to September 2022 were included in the study and divided into two groups: Enhanced Recovery After Surgery (ERAS) and non-ERAS. Data on postoperative inflammatory markers and complications were also collected. RESULTS: A total of 313 patients with colorectal cancer were included: 182 in the ERAS group and 131 in the non-ERAS group. The patients in the ERAS group had significantly shorter days of postoperative hospitalization, urinary catheter and drainage tube withdrawal times, and recovery of bowel function (P < .05) than those of the non-ERAS group. Moreover, the ERAS group had lower hospitalization expenses than those of the non-ERAS group (P < .05). However, the procalcitonin and tumor necrosis factor (TNF)-α levels in the ERAS group was significantly lower than those in the non-ERAS group on postoperative days 1 and 3 (P < .05), and the interleukin (IL)-6 and IL-10 levels in the ERAS group were significantly lower than those in the non-ERAS group on the 1st, 3rd, and 5th postoperative days (P < .05). The C-reactive protein (CRP) and white blood cell (WBC) levels in the ERAS group were lower than those in the non-ERAS group on postoperative days 3 and 5 (P < .05). However, the hemoglobin levels did not differ significantly (P > .05). The albumin levels did not differ significantly between the two groups before surgery (P > .05); however, the albumin level in the ERAS group was higher than that in the non-ERAS group on postoperative days 3 and 5 (P < .05). The ERAS patients had lower albumin levels after surgery than those of the non-ERAS patients (P < .05). CONCLUSION: ERAS leads to a series of perioperative optimization measures, thereby reducing the postoperative stress response in elderly patients with colorectal cancer and the occurrence of perioperative complications.

rgpA-Engineered/Functionalized DNA Vaccine as a Novel Prophylactic Vaccination to Prevent Porphyromonas gingivalis-Induced Periodontitis: An in Vivo Study.

BACKGROUND: Arg-gingipain A (rgpA) and Arg-gingipain B (rgpB) are crucial virulence factors associated with Porphyromonas gingivalis (P. gingivalis) and have been recognized as promising targets for antibacterial vaccines. Although vaccines containing rgpA have shown efficacy, the incorporation of rgpB, which lacks the haemagglutinin adhesin (HA) domain, diminishes the vaccine's effectiveness. This study aims to assess the immunogenicity of the functional HA domain of rgpA in mouse periodontitis models. METHODS: A total of 24 mice were randomly divided into four groups, each receiving different immune injections: group A received phosphate-buffered saline (PBS) as an empty control; group B received pVAX1 as a negative control (NC); group C received pVAX1-HA; and group D received pVAX1-rgpA. The mice were subjected to intramuscular injections every two weeks for a total of three administrations. Prior to each immunization, blood samples were collected for antibody detection under isoflurane anesthesia. Following the final immunization, periodontitis was induced two weeks later by using sutures soaked in a P. gingivalis solution. The mice were euthanized after an additional two-week period. To assess the safety of the procedure, major organs were examined through hematoxylin-eosin (HE) staining. Subsequently, the levels of IgG, IgG1, and IgG2a in the serum were quantified via enzyme-linked immunosorbent assay (ELISA). Additionally, the expression of inflammatory factors in the gingiva, including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor alpha (TNF-α), was determined using quantitative real-time reverse transcript PCR (qRT-PCR). The extent of bone loss in periodontal tissues was evaluated using micro-computed tomography (micro-CT) and HE staining. RESULTS: HE staining of the organs confirmed the absence of vaccine-induced toxicity in vivo. After the second immunization, both the rgpA and HA groups displayed significantly higher specific IgG titers in comparison to the NC and PBS groups (p < 0.05). Furthermore, the rgpA and HA groups exhibited a noteworthy predominance of IgG1 antibodies after three immunization doses, while there was a noticeable reduction in IgG2a levels observed following ligation with P. gingivalis sutures, as opposed to the NC and PBS groups (p < 0.05). Additionally, both the HA and rgpA groups showed a significant decrease in the expression of inflammatory factors such as IL-6, IL-1ß, and TNF-α, as well as a reduction in bone loss around periodontitis-affected teeth, when compared to the NC and PBS groups (p < 0.05). CONCLUSIONS: The results of this study demonstrate that the rgpA-engineered/functionalized HA gene vaccine is capable of eliciting a potent prophylactic immune response against P. gingivalis-induced periodontitis, effectively serving as an immunogenic and protective agent in vivo.