The prognostic value of the combined neutrophil-to-lymphocyte ratio (NLR) and neutrophil-to-platelet ratio (NPR) in sepsis.

Sepsis is a severe disease characterized by high mortality rates. Our aim was to develop an early prognostic indicator of adverse outcomes in sepsis, utilizing easily accessible routine blood tests. A retrospective analysis of sepsis patients from the MIMIC-IV database was conducted. We performed univariate and multivariate regression analyses to identify independent risk factors associated with in-hospital mortality within 28 days. Logistic regression was utilized to combine the neutrophil-to-lymphocyte ratio (NLR) and the neutrophil-to-platelet ratio (NPR) into a composite score, denoted as NLR_NPR. We used ROC curves to compare the prognostic performance of the models and Kaplan-Meier survival curves to assess the 28 day survival rate. Subgroup analysis was performed to evaluate the applicability of NLR_NPR in different subpopulations based on specific characteristics. This study included a total of 1263 sepsis patients, of whom 179 died within 28 days of hospitalization, while 1084 survived beyond 28 days. Multivariate regression analysis identified age, respiratory rate, neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-platelet ratio (NPR), hypertension, and sequential organ failure assessment (SOFA) score as independent risk factors for 28 day mortality in septic patients (P < 0.05). Additionally, in the prediction model based on blood cell-related parameters, the combined NLR_NPR score exhibited the highest predictive value for 28 day mortality (AUC = 0.6666), followed by NLR (AUC = 0.6456) and NPR (AUC = 0.6284). Importantly, the performance of the NLR_NPR score was superior to that of the commonly used SOFA score (AUC = 0.5613). Subgroup analysis showed that NLR_NPR remained an independent risk factor for 28 day in-hospital mortality in the subgroups of age, respiratory rate, and SOFA, although not in the hypertension subgroup. The combined use of NLR and NPR from routine blood tests represents a readily available and reliable predictive marker for 28 day mortality in sepsis patients. These results imply that clinicians should prioritize patients with higher NLR_NPR scores for closer monitoring to reduce mortality rates.

Polyethylene imine-modified photonic crystal microfluidic chip for highly sensitive detection of microbial spores.

To address the lengthy cycles, complex operations, high costs, and insufficient sensitivity of biomarker detection in traditional biological control agents, photonic crystal treated with PEI was developed for highly sensitive detection of Sclerotinia sclerotiorum microbial spores. By incorporating gelatin molecules, photonic crystal is endowed with excellent photothermal stability and high stability in aqueous solutions. The photonic crystal surface is conferred a positive charge by PEI, which can be used to enhance the adsorption of spores. Efficient enrichment of Sclerotinia sclerotiorum and Purpureocillium lilacinum spores is achieved, with coefficients of determination (RYe et al. (2014)2) 0.963 and 0.971, respectively. The detection range is from 102 to 106 spores/ml, and the photonic crystal exhibited good reusability. The prepared photonic crystal enables rapid, non-destructive, and accurate quantitative detection of microbial spores.

Comparison of vonoprazan bismuth-containing triple therapy with quadruple therapy in Helicobacter pylori-infected treatment-naive patients: a prospective multicenter randomized controlled trial.

BACKGROUND AND AIM: Helicobacter pylori infection is linked to various gastrointestinal conditions, such as chronic active gastritis, peptic ulcers, and gastric cancer. Traditional treatment options encounter difficulties due to antibiotic resistance and adverse effects. Therefore, the aim of this study was to explore the effectiveness of a new treatment plan that combines vonoprazan (VPZ), amoxicillin, and bismuth for the eradication of H. pylori. METHODS: A total of 600 patients infected with H. pylori were recruited for this multicenter randomized controlled trial. Patients treated for H. pylori elimination were randomly assigned at a 1:1 ratio to receive 14 days of vonoprazan-based triple therapy (vonoprazan + amoxicillin + bismuth, group A) or standard quadruple therapy (esomeprazole + clarithromycin + amoxicillin + bismuth, group B). Compliance and adverse effects were tracked through daily medication and side effect records. All patients underwent a 13C/14C-urea breath test 4 weeks after treatment completion. RESULTS: Intention-to-treat (ITT) and per-protocol (PP) analyses revealed no substantial differences in H. pylori eradication rates between groups A and B (ITT: 83.7% vs 83.2%; PP: 90.9% vs 89.7%). However, significant differences were observed in the assessment of side effects (13.7% vs 28.6%, P < 0.001). Specifically, group A had significantly fewer "bitter mouths" than group B did (3.7% vs 16.2%, P < 0.001). CONCLUSION: Triple therapy comprising vonoprazan (20 mg), amoxicillin (750 mg), and bismuth potassium citrate (220 mg) achieved a PP eradication rate ≥90%, paralleling standard quadruple therapy, and had fewer adverse events and lower costs (¥306.8 vs ¥645.8) for treatment-naive patients.

OTULIN deficiency: focus on innate immune system impairment.

OTULIN deficiency is a complex disease characterized by a wide range of clinical manifestations, including skin rash, joint welling, lipodystrophy to pulmonary abscess, and sepsis shock. This disease is mechanistically linked to mutations in the OTULIN gene, resulting in an immune disorder that compromises the body's ability to effectively combat pathogens and foreign stimuli. The OTULIN gene is responsible for encoding a deubiquitinating enzyme crucial for hydrolyzing Met1-poly Ub chains, and its dysfunction leads to dysregulated immune responses. Patients with OTULIN deficiency often exhibit an increase in monocytes, including neutrophils and macrophages, along with inflammatory clinical features. The onset of symptoms typically occurs at an early age. However, individuals with OTULIN haploinsufficiency are particularly susceptible to life-threatening staphylococcal infections. Currently, the most effective treatment for patients with OTULIN biallelic mutations involves the use of TNF-blocking agents, which target the dysregulated immune response. In conclusion, OTULIN deficiency presents a complex clinical picture with diverse manifestations, attributed to mutations in the OTULIN gene. Understanding the underlying mechanisms is crucial for developing targeted therapeutic interventions to address this challenging condition. Further research into the pathophysiology of OTULIN deficiency is essential for improving clinical management and outcomes for affected individuals.

[Mechanism of Fuzheng Huayu Tablets against hepatic fibrosis based on transcriptome and single-cell sequencing].

This study aimed to investigate the role of macrophage polarization in the treatment of liver fibrosis by Fuzheng Huayu Tablets(FZHY) through single-cell, transcriptome sequencing and in vitro and in vivo experiments. Liver fibrosis-related datasets, transcriptomic datasets, and single-cell sequencing datasets were obtained from the Gene Expression Omnibus(GEO) database to screen differential genes. Liver fibrosis-related genes were obtained from GeneCards, DisGeNET, NCBI, PharmgKB, TTD and OMIM databases. Macrophage polarization-related genes were obtained from the GeneCards database. The above three gene sets were intersected to construct a protein-protein interaction(PPI) network. Cytoscape software was used to screen core proteins, and the expression pattern of core proteins was visualized by single-cell sequencing. A mouse model of liver fibrosis was constructed using carbon tetrachloride(CCl_4). Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological morphology of liver tissues. The expressions of α-smooth muscle actin(α-SMA) and transforming growth factor-ß1(TGF-ß1) were detected by immunohistochemistry. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected by colorimetry. The le-vels of inflammatory factors in serum were detected by the enzyme-linked immunosorbent assay(ELISA). Furthermore, the expressions of α-SMA, TGF-ß1, cluster of differentiation 86(CD86) and thrombospondin 1(THBS1) in liver tissues were detected by Western blot(WB). Lipopolysaccharide(LPS) was used to stimulate RAW264.7 cells to construct the M1 macrophage polarization model. The cell counting kit-8(CCK-8) method was used to detect cell viability. WB was used to detect the protein expressions of CD86 and THBS1 in cells, and the messenger ribonucleic acid(mRNA) expression levels of tumor necrosis factor-α(TNF-α) and interleukin(IL)-1ß by real-time fluorescent quantitative reverse transcription polymerase chain reaction(RT-qPCR). The results showed that a total of 26 potential genes related to the polarization of liver fibrosis macrophages were obtained, and 10 core proteins related to the polarization of liver fibrosis macrophages such as THBS1, lumican(LUM) and fibulin-5(FBLN5) were screened. Single-cell data analysis indicated that THBS1, ranking highest, may be expressed by M1 macrophages. Animal experiments demonstrated that FZHY reduced inflammatory cell infiltration and collagen deposition in CCl_4-induced mouse liver, relieved liver injury and inflammation levels, and inhibited the expressions of α-SMA, TGF-ß1, CD86, and THBS1 proteins. Cell experiments revealed that FZHY significantly reduced intracellular expression of CD86 and THBS1 proteins and mRNA levels of TNF-α and IL-1ß. In conclusion, FZHY may ameliorate liver fibrosis by inhibiting THBS1 protein expression, suppressing M1 macrophage polarization, and reducing inflammation.

Advancing burn wound treatment: exploring hydrogel as a transdermal drug delivery system.

Burn injuries are prevalent and life-threatening forms that contribute significantly to mortality rates due to associated wound infections. The management of burn wounds presents substantial challenges. Hydrogel exhibits tremendous potential as an ideal alternative to traditional wound dressings such as gauze. This is primarily attributed to its three-dimensional (3D) crosslinked polymer network, which possesses a high water content, fostering a moist environment that supports effective burn wound healing. Additionally, hydrogel facilitates the penetration of loaded therapeutic agents throughout the wound surface, combating burn wound pathogens through the hydration effect and thereby enhancing the healing process. However, the presence of eschar formation on burn wounds obstructs the passive diffusion of therapeutics, impairing the efficacy of hydrogel as a wound dressing, particularly in cases of severe burns involving deeper tissue damage. This review focuses on exploring the potential of hydrogel as a carrier for transdermal drug delivery in burn wound treatment. Furthermore, strategies aimed at enhancing the transdermal delivery of therapeutic agents from hydrogel to optimize burn wound healing are also discussed.

VEGF and EGFR signaling pathways are involved in the baicalein attenuation of OVA-induced airway inflammation and airway remodeling in mice.

BACKGROUND: Although Traditional Chinese Medicine (TCM) has been used for treating asthma for centuries, the understanding of its mechanism of action is still limited. Thus, the purpose of this study was to explore the possible therapeutic effects, and underlying mechanism of baicalein in the treatment of asthma. METHODS: Freely availabled atabases (e.g. OMIM, TTD, Genecards, BATMAN-TCM, STITCH 5.0, SEA, SwissTargetPrediction) and software (e.g. Ligplot 2.2.5 and PyMoL) were used for disease drug target prediction and molecular docking by network pharmacology. The efficacy and mechanism of action of baicalein in the treatment of asthma were validated using an ovalbumin (OVA)-induced asthma mouse model and molecular biology techniques. RESULTS: A total of 1655 asthma-related genes and 161 baicalein-related targets were identified from public databases. Utilizing common databases and software for network pharmacology and molecular docking analysis, seven potential target proteins for the therapeutic effects of baicalein on asthma were selected, including v-akt murine thymoma viral oncogene homolog 1 (AKT1), vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC), mitogen-activated protein kinase 3 (MAPK3), matrix metallopeptidase 9 (MMP9), and MAPK1. In vivo, baicalein treatment via intraperitoneal injection at a dose of 50 mg/kg significantly reduced airway inflammation, collagen deposition, smooth muscle thickness, lung interleukin (IL)-4 and IL-13 levels, peripheral blood immunoglobulin (Ig)E levels, as well as the count and ratio of eosinophils in bronchoalveolar lavage fluid (BALF) in an OVA-induced asthma mouse model. Further validation by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting analysis revealed that the VEGF and EGFR signaling pathways involving VEGFA, MAPK1, MAPK3, and EGFR were inhibited by baicalein in the asthma mouse model. CONCLUSION: Baicalein attenuates airway inflammation and airway remodeling through inhibition of VEGF and EGFR signaling pathways in an OVA-induced asthma mouse model. This will provide a new basis for the development of baicalein as a treatment for asthma and highlights the potential of network pharmacology and molecular docking in drug discovery and development.

Impact of filial piety on residents' subjective well-being in China considering the moderating effect of income level.

Subjective well-being (SWB) reflects an individual's subjective evaluation of overall life satisfaction and healthcare situation. As one of the most important concepts in traditional Chinese culture, filial piety refers to an ancient and significant ethical concept that originates from traditional Chinese culture. Filial piety emphasizes the respect, care, and filial devotion of children towards their parents, and has a complex influence on SWB. Moreover, in the context of rapid economic development, an individual's income level significantly moderates the influence of filial piety. Revealing the influence of different types of filial piety on SWB is of great significance for enhancing residents' SWB. However, existing studies rarely touch upon this topic. Therefore, this paper focuses on the 7 kinds of filial piety, establishes an ordered logit model based on the data from the China General Social Survey, and analyzes the influence of these 7 kinds of filial piety on SWB. On this basis, this study analyzes the moderating effect of income level. Finally, it further analyzes the regional heterogeneity of China in the influence of filial piety. Concepts such as constant respect for father's authority, enhancing parents' honor, and bearing sons for the purpose of lineage continuity, have negative impact on SWB. Superior economic conditions can neutralize and salvage these concepts to a certain extent, but they are ultimately negative. In regions with a minority population such as the 4 northeastern provinces, Inner Mongolia, Gansu, Ningxia, and Xinjiang, these concepts can increase SWB, which is restricted by the local economic level and might just be a transitional form of insufficient development. appreciating the kindness of upbringing; treating parents well under any circumstances; giving up personal ambitions to fulfill parents' wishes, positively influence individual SWB, especially when income is substantial. The research results indicate that different type of filial piety has different impacts on SWB; income level has a significant moderating effect; and there are significant regional heterogeneities in the influence of filial piety. The results of this study provide a theoretical basis and reference for enhancing residents' SWB.

Liquid-liquid phase separation-related lncRNA prognostic signature and ZNF32-AS2 as a novel biomarker in hepatocellular carcinoma.

BACKGROUND: Liquid-liquid phase separation (LLPS) enhances oncogenic signaling pathways and advances cancer progression, and has been proposed as a promising cancer biomarker and intervention target. Nevertheless, doubts remain about the prognostic importance of LLPS-related long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC). METHODS: An LLPS-related lncRNA prognostic signature was generated by drivers and regulators of LLPS, and was validated in external datasets. The underlying genetic changes and functional enrichment of the signature were assessed. The drug sensitivity and response to immunotherapy were predicted in patients categorized as high-risk and low-risk. Clinical samples, phase separation agonist, and dispersant were used to identify lncRNAs with the most significant expression change. Cancer cells with ZNF32-AS2 expression regulation were subjected to colony formation assay, scratch test assay, migration and invasion assay, sorafenib resistance assay, and xenograft tumor model. RESULTS: The signature of LLPS-related hub lncRNAs identified through Weighted Gene Co-Expression Network Analysis showed outstanding performance in training and external validation cohorts consistently, and the molecular characteristics varied between different risk groups. Potential drugs for high-risk individuals were identified, and low-risk individuals demonstrated a more favorable reaction to immunotherapy. ZNF32-AS2 showed the most significant expression change in phase separation agonist and dispersant treatment. ZNF32-AS2 promoted the proliferation, mobility, and sorafenib resistance of liver cancer cells. CONCLUSIONS: The LLPS-related lncRNA signature may help assess prognosis and predict treatment efficacy in clinical settings. LLPS-related ZNF32-AS2 promoted the proliferation, mobility, and sorafenib resistance of liver cancer cells, and may be a novel potential biomarker in hepatocellular carcinoma.

Comparison of the surgical outcomes of the posterior approach, video-assisted thoracic surgery, and combined approach for thoracic dumbbell tumors based on a new classification: a retrospective study.

The appropriate surgical treatment strategy was based on the regions of tumor invasion. There is no classification to aid the surgeon in selection. A retrospective study of the clinical data of patients who underwent resection of thoracic dumbbell tumors at the Neurosurgery and Thoracic Surgery Department of Hospital between January 1, 2016, and December 31, 2021 was conducted. Patient data, images, and surgical outcome data were collected. The thoracic spine was divided into areas A, B, and C with respect to the line through the middle of the intervertebral foramen and the line of the costo-transverse joint lateral margin in the horizontal plane. Type I tumors were located in areas A or A and B, type II tumors were located in areas B or B and C, and type III tumors were located in areas A, B, and C. Fifty-five patients with thoracic dumbbell tumors were surgically treated (mean age, 43.1 years; 22 (40%) female). The patients with type I and III tumors underwent the posterior approach, type III tumors had more bleeding during the operation and longer operation times than type I. Among the patients with type II tumors who underwent video-assisted thoracic surgery and the posterior approach, the posterior group had more bleeding and a longer operation time than the others. The patients with type III tumors underwent the combined approach and the posterior approach; although there was no clear difference in the bleeding volume or operation time, the combined approach group had a lower incidence of complications. The new classification of different types of thoracic dumbbell tumors can simply and effectively guide the selection of surgery.

Exosome-derived tRNA fragments tRF-GluCTC-0005 promotes pancreatic cancer liver metastasis by activating hepatic stellate cells.

Early metastasis is the primary factor in the very poor prognosis of pancreatic ductal adenocarcinoma (PDAC), with liver metastasis being the most common form of distant metastasis in PDAC. To investigate the mechanism of PDAC liver metastasis, we found that PDAC cells can promote the formation of pre-metastatic niches (PMNs) through exosomes to facilitate liver metastasis in the early stage. In our study, hepatic stellate cells (HSCs) were treated with PDAC-derived exosomes (PDAC-exo), and the activation of HSCs was detected. A novel transfer RNA-derived fragment, the tRF-GluCTC-0005 was obtained by small RNA sequencing from serum exosomes of PDAC patients. Bioinformatics analysis and RNA pull-down assays revealed the interaction between WDR1 and tRF-GluCTC-0005. A KPC transgenic mouse model and an AAV-mediated sh-WDR1 mouse model were used to detect the mechanism of liver metastasis in vivo. Finally, the dual luciferase reporter assay, protein mutation truncation assay, Co-IP assay, and flow cytometry assay were used to explore the molecular mechanism in HSCs activation and PMNs formation. We found that the tRF-GluCTC-0005 in exosomes binds to the 3' untranslated region of the mRNA of the WDRl in HSCs and increases mRNA stability. The N-terminals of WDR1 bind to the YAP protein directly, inhibit YAP phosphorylation, and promote the expression of YAP transcription factors. The tRF-GluCTC-0005 in PDAC-exo significantly recruits myeloid-derived suppressor cells (MDSCs) in the liver, creating a PMNs immunosuppressive microenvironment and further advancing liver metastasis from PDAC. Our results suggest that the key of PDAC liver metastasis is the activation of HSCs through upregulation of WDR1 by tRF-GluCTC-0005 in exosomes, which mediates the infiltration of MDSCs to form PMNs.

HIV-1 binds dynein directly to hijack microtubule transport machinery.

Viruses exploit host cytoskeletal elements and motor proteins for trafficking through the dense cytoplasm. Yet the molecular mechanism that describes how viruses connect to the motor machinery is unknown. Here, we demonstrate the first example of viral microtubule trafficking from purified components: HIV-1 hijacking microtubule transport machinery. We discover that HIV-1 directly binds to the retrograde microtubule-associated motor, dynein, and not via a cargo adaptor, as previously suggested. Moreover, we show that HIV-1 motility is supported by multiple, diverse dynein cargo adaptors as HIV-1 binds to dynein light and intermediate chains on dynein's tail. Further, we demonstrate that multiple dynein motors tethered to rigid cargoes, like HIV-1 capsids, display reduced motility, distinct from the behavior of multiple motors on membranous cargoes. Our results introduce a new model of viral trafficking wherein a pathogen opportunistically 'hijacks' the microtubule transport machinery for motility, enabling multiple transport pathways through the host cytoplasm.

Foam nickel-PDMS composite film based triboelectric nanogenerator for speed and acceleration sensing.

As a new energy conversion technology, triboelectric nanogenerator (TENG) can use the coupling of triboelectrification and electrostatic induction effect to convert tiny mechanical energy into electrical energy, powering small electronic devices. In this paper, a vibration sensing triboelectric nanogenerator (V-TENG) based on a foam nickel-PDMS composite film was prepared, which can convert low frequency and small-amplitude mechanical energy into electrical energy, and the open circuit voltage of V-TENG can reach 3.6V at a vibration frequency of 4 Hz. In addition, the V-TENG can be used as a self-powered speed/acceleration sensor to detect speed changes in the range of 0.3 m/s to 1.5 m/s and acceleration changes in the range of 3 m/s2 to 13 m/s2.

The cotton MYB33 gene is a hub gene regulating the trade-off between plant growth and defense in Verticillium dahliae infection.

INTRODUCTION: Sessile plants engage in trade-offs between growth and defense capacity in response to fluctuating environmental cues. MYB is an important transcription factor that plays many important roles in controlling plant growth and defense. However, the mechanism behind how it keeps a balance between these two physiological processes is still largely unknown. OBJECTIVES: Our work focuses on the dissection of the molecular mechanism by which GhMYB33 regulates plant growth and defense. METHODS: The CRISPR/Cas9 technique was used to generate mutants for deciphering GhMYB33 functions. Yeast two-hybrid, luciferase complementary imaging, and co-immunoprecipitation assays were used to prove that proteins interact with each other. We used the electrophoretic mobility shift assay, yeast one-hybrid, and luciferase activity assays to analyze GhMYB33 acting as a promoter. A ß-glucuronidase fusion reporter and 5' RNA ligase mediated amplification of cDNA ends analysis showed that ghr-miR319c directedly cleaved the GhMYB33 mRNA. RESULTS: Overexpressing miR319c-resistant GhMYB33 (rGhMYB33) promoted plant growth, accompanied by a significant decline in resistance against Verticillium dahliae. Conversely, its knockout mutant, ghmyb33, demonstrated growth restriction and concomitant augmentation of V. dahliae resistance. GhMYB33 was found to couple with the DELLA protein GhGAI1 and bind to the specific cis-elements of GhSPL9 and GhDFR1 promoters, thereby modulating internode elongation and plant resistance in V. dahliae infection. The ghr-miR319c was discovered to target and suppress GhMYB33 expression. The overexpression of ghr-miR319c led to enhanced plant resistance and a simultaneous reduction in plant height. CONCLUSION: Our findings demonstrate that GhMYB33 encodes a hub protein and controls the expression of GhSPL9 and GhDFR1, implicating a pivotal role for the miR319c-MYB33 module to regulate the trade-offs between plant growth and defense.

Open source board based acoustofluidic transwells for reversible disruption of the blood-brain barrier for therapeutic delivery.

BACKGROUND: Blood-brain barrier (BBB) is a crucial but dynamic structure that functions as a gatekeeper for the central nervous system (CNS). Managing sufficient substances across the BBB is a major challenge, especially in the development of therapeutics for CNS disorders. METHODS: To achieve an efficient, fast and safe strategy for BBB opening, an acoustofluidic transwell (AFT) was developed for reversible disruption of the BBB. The proposed AFT was consisted of a transwell insert where the BBB model was established, and a surface acoustic wave (SAW) transducer realized using open-source electronics based on printed circuit board techniques. RESULTS: In the AFT device, the SAW produced acousto-mechanical stimulations to the BBB model resulting in decreased transendothelial electrical resistance in a dose dependent manner, indicating the disruption of the BBB. Moreover, SAW stimulation enhanced transendothelial permeability to sodium fluorescein and FITC-dextran with various molecular weight in the AFT device. Further study indicated BBB opening was mainly attributed to the apparent stretching of intercellular spaces. An in vivo study using a zebrafish model demonstrated SAW exposure promoted penetration of sodium fluorescein to the CNS. CONCLUSIONS: In summary, AFT effectively disrupts the BBB under the SAW stimulation, which is promising as a new drug delivery methodology for neurodegenerative diseases.

An ultrasound-activatable platinum prodrug for sono-sensitized chemotherapy.

Despite the great success achieved by photoactivated chemotherapy, eradicating deep tumors using external sources with high tissue penetration depth remains a challenge. Here, we present cyaninplatin, a paradigm of Pt(IV) anticancer prodrug that can be activated by ultrasound in a precise and spatiotemporally controllable manner. Upon sono-activation, mitochondria-accumulated cyaninplatin exhibits strengthened mitochondrial DNA damage and cell killing efficiency, and the prodrug overcomes drug resistance as a consequence of combined effects from released Pt(II) chemotherapeutics, the depletion of intracellular reductants, and the burst of reactive oxygen species, which gives rise to a therapeutic approach, namely sono-sensitized chemotherapy (SSCT). Guided by high-resolution ultrasound, optical, and photoacoustic imaging modalities, cyaninplatin realizes the overall theranostics of tumors in vivo with superior efficacy and biosafety. This work highlights the practical utility of ultrasound to precisely activate Pt(IV) anticancer prodrugs for the eradication of deep tumor lesions and broadens the biomedical uses of Pt coordination complexes.

The impact of postoperative radiotherapy on the survival of patients with stage III non-small cell lung cancer: A CONSORT-compliant analysis using the SEER database.

BACKGROUND: Postoperative radiotherapy (PORT) is commonly used to treat patients with resected stage III non-small cell lung cancer (NSCLC), but its effectiveness remains uncertain. This retrospective cohort study aimed to investigate the impact of PORT on overall survival (OS) and evaluate its heterogeneity among subgroups of patients. METHODS: A total of 6305 patients with resected stage III NSCLC were included in this study from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching was conducted to balance baseline characteristics between the patients who received PORT and those who did not. OS was used as the primary outcome. Subgroup analysis was performed to identify which patient subgroups might benefit more from PORT. RESULTS: Overall, no significant difference was observed in OS between the 2 groups with or without propensity score matching. However, subgroup analysis demonstrated that PORT improved OS in patients with certain characteristics, including stage IIIA/N2, stage IIIB, squamous cell carcinoma, tumor grade III-IV, or lymph node ratio (LNR) > 1/3. Multivariate analysis showed that several variables were associated with adverse prognostic factors for OS, such as marital status (others), race (white), male gender, squamous cell carcinoma, elderly age, advanced stage, poor histological differentiation grade, high LNR, and not receiving chemotherapy. CONCLUSION: In patients with resected stage III NSCLC, PORT may not be beneficial for all patients. However, it may improve survival time in certain patient subgroups, such as those with stage IIIA/N2, stage IIIB, squamous cell carcinoma, tumor grade III to IV, or LNR > 1/3. These findings provide important information for clinical decision-making and future research regarding the use of PORT in patients with resected stage III NSCLC.

Optimizing retrieval spaces of bio-optical models for remote sensing of ocean color.

We investigated the optimal number of independent parameters required to accurately represent spectral remote sensing reflectances (R rs) by performing principal component analysis on quality controlled in situ and synthetic R rs data. We found that retrieval algorithms should be able to retrieve no more than four free parameters from R rs spectra for most ocean waters. In addition, we evaluated the performance of five different bio-optical models with different numbers of free parameters for the direct inversion of in-water inherent optical properties (IOPs) from in situ and synthetic R rs data. The multi-parameter models showed similar performances regardless of the number of parameters. Considering the computational cost associated with larger parameter spaces, we recommend bio-optical models with three free parameters for the use of IOP or joint retrieval algorithms.

The stromal-tumor amplifying STC1-Notch1 feedforward signal promotes the stemness of hepatocellular carcinoma.

BACKGROUND: Cancer-associated fibroblasts (CAFs), an important component of the tumor microenvironment (TME), play crucial roles in tumor stemness. It has been shown in various cancer studies that stanniocalcin-1 (STC1) is secreted by CAFs, however, its function in HCC is still not clear. METHODS: The serum concentration and intracellular expression level of STC1 were quantified by ELISA and western blotting, respectively. The role of CAF-derived STC1 in HCC stemness was investigated by sphere formation, sorafenib resistance, colony formation, and transwell migration and invasion assays in vitro and in an orthotopic liver xenograft model in vivo. An HCC tissue microarray containing 72 samples was used to evaluate the expression of STC1 and Notch1 in HCC tissues. Coimmunoprecipitation (CoIP) and dual-luciferase reporter assays were performed to further explore the underlying mechanisms. ELISAs were used to measure the serum concentration of STC1 in HCC patients. RESULTS: We demonstrated that CAFs were the main source of STC1 in HCC and that CAF-derived STC1 promoted HCC stemness through activation of the Notch signaling pathway. In HCC patients, the expression of STC1 was positively correlated with Notch1 expression and poor prognosis. The co-IP assay showed that STC1 directly bound to Notch1 receptors to activate the Notch signaling pathway, thereby promoting the stemness of HCC cells. Our data further demonstrated that STC1 was a direct transcriptional target of CSL in HCC cells. Furthermore, ELISA revealed that the serum STC1 concentration was higher in patients with advanced liver cancer than in patients with early liver cancer. CONCLUSIONS: CAF-derived STC1 promoted HCC stemness via the Notch1 signaling pathway. STC1 might serve as a potential biomarker for the prognostic assessment of HCC, and the stromal-tumor amplifying STC1-Notch1 feedforward signal could constitute an effective therapeutic target for HCC patients.