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In this study, a turn-on fluorescence sensor for the detection of adenosine 5′-triphosphate (ATP) was developed and tested using ATP-DNA2-Ag NCs. The results showed that the fluorescence of ATP-DNA2-Ag NCs was significantly enhanced with the addition of ATP. The fluorescence enhancement was a result of the specific binding activity of the ATP aptamer and ATP, which caused G-rich sequences to approach the dark DNA-Ag NCs, owing to the alteration in ATP aptamer conformation. The proposed sensor demonstrated a good linear range of 18–42 mM and a limit of detection (LOD) of 2.8 μM. The sensor's features include sensitivity, selectivity, and simple operation. In addition, the proposed sensor successfully measured ATP in 100-fold diluted fetal bovine serum. [ABSTRACT FROM AUTHOR]

In this study, Cu2+ modulated silver nanoclusters were constructed for the turn-on, label-free detection of L-histidine. Six Ag NCs protected by oligonucleotides (DNA-Ag NCs) were tested in a series of experiments. Finally, A-DAN-Ag NCs were chosen as the best candidate due to their excellent fluorescent properties. The fluorescence of A-DAN-Ag NCs was quenched using Cu2+ through energy or electron transfer. However, quenched fluorescence could be restored dramatically in the presence of L-histidine due to Cu2+ liberation from A-DAN-Ag NCs and because of the chelation between the imidazole group of L-histidine and Cu2+. The proposed sensor exhibited high selectivity towards L-histidine over other amino acids, with a limit of detection (LOD) of 0.096 μM ranging from 0 to 8 μM. The proposed sensor succeeded in detecting L-histidine in diluted human urine. Therefore, the sensor has promising practical applications in biological systems. [ABSTRACT FROM AUTHOR]

As an important endogenous gasotransmitter, hydrogen sulfide (H2S) plays a critical role in various physiological functions and has been regarded as a biomarker of cancer due to its overexpression in cancer cells. In addition, the early stages of cancer are often accompanied by abnormalities in the intracellular microenvironments, and distinguishing between cancer cell/tissues and normal cell/tissues is of great significance to the accuracy of cancer diagnosis. However, deep insights into the simultaneous detection of H2S and viscosity/polarity variations in cancer cells/tissues are rarely reported. In this work, we designed and synthesized a mitochondria-targeting fluorescent probe PDQHS, which exhibits high selectivity for H2S with an emission peak around 632 nm and excellent response (17-fold) to viscosity/polarity beyond 706 nm. Meanwhile, PDQHS shows good biocompatibility and can specifically accumulate into mitochondria. Using PDQHS, the visual distinguishing of cancer cells from normal cells was achieved via dual-channel detection of H2S and viscosity/polarity. More importantly, PDQHS has been successfully applied to visualize endogenous and exogenous H2S in living cells and tumor tissue. Obviously, compared to the detection of a single biomarker, monitoring multiple biomarkers simultaneously through dual-channel response is conducive to amplifying the detection signal, providing a more sensitive and reliable imaging tool in the tumor region, which is beneficial for cancer prediction. [ABSTRACT FROM AUTHOR]

Introduction: Low‐level pressure support ventilation (PSV) is most commonly adopted in spontaneous breathing trials (SBTs), and some have proposed setting the positive end‐expiratory pressure (PEEP) to 0 cmH2O in order to shorten the observation time of SBTs. This study aims to investigate the effects of two PSV protocols on the patients' respiratory mechanics. Material and method: A prospective randomized self‐controlled crossover design was adopted in this study, which involved enrolling 30 difficult‐to‐wean patients who were admitted to the intensive care unit of the First Affiliated Hospital of Guangzhou Medical University between July 2019 and September 2021. Patients were subjected to the S group (pressure support: 8 cmH2O, PEEP: 5 cmH2O) and S1 group (PS: 8 cmH2O, PEEP: 0 cmH2O) for 30 min in a random order, and respiratory mechanics indices were dynamically monitored via a four‐lumen multi‐functional catheter with an integrated gastric tube. Among the 30 enrolled patients, 27 were successfully weaned. Result: The S group showed higher airway pressure (Paw), intragastric pressure (Pga) and airway pressure–time product (PTP) than the S1 group. The S group also showed a shorter inspiratory trigger delay, (93.80 ± 47.85) versus (137.33 ± 85.66) ms (P = 0.004); and fewer abnormal triggers, (0.97 ± 2.65) versus (2.67 ± 4.48) (P = 0.042) compared with the S1 group. Stratification based on the causes of mechanical ventilation revealed that under the S1 protocol, patients with chronic obstructive pulmonary disease (COPD) had a longer inspiratory trigger delay compared to both post‐thoracic surgery (PTS) patients and patients with acute respiratory distress syndrome. Despite providing greater respiratory support, S group led to significant reductions in inspiratory trigger delay and less abnormal triggers compared to S1 group, especially among patients with chronic obstructive pulmonary disease. Conclusion: These findings suggest that the zero PEEP group was more likely to induce a higher number of patient–ventilator asynchronies in difficult‐to‐wean patients. [ABSTRACT FROM AUTHOR]

Wheat production is often impacted by pre-winter freezing damage and cold spells in later spring. To study the influences of cold stress on wheat seedlings, unstressed Jing 841 was sampled once at the seedling stage, followed by 4 °C stress treatment for 30 days and once every 10 days. A total of 12,926 differentially expressed genes (DEGs) were identified from the transcriptome. K-means cluster analysis found a group of genes related to the glutamate metabolism pathway, and many genes belonging to the bHLH, MYB, NAC, WRKY, and ERF transcription factor families were highly expressed. Starch and sucrose metabolism, glutathione metabolism, and plant hormone signal transduction pathways were found. Weighted Gene Co-Expression Network Analysis (WGCNA) identified several key genes involved in the development of seedlings under cold stress. The cluster tree diagram showed seven different modules marked with different colors. The blue module had the highest correlation coefficient for the samples treated with cold stress for 30 days, and most genes in this module were rich in glutathione metabolism (ko00480). A total of eight DEGs were validated using quantitative real-time PCR. Overall, this study provides new insights into the physiological metabolic pathways and gene changes in a cold stress transcriptome, and it has a potential significance for improving freezing tolerance in wheat. [ABSTRACT FROM AUTHOR]

A new hybrid organic–inorganic perovskite, (R-3AQ)KI3 [R-3AQ2+ = (R)-(+)-3-aminoquinuclidine], has been synthesized and comprehensively characterized by experimental approaches and density functional theory calculations. Our experimental results demonstrate that (R-3AQ)KI3 has a typical perovskite structure and exhibits a reversible order–disorder phase transition at temperatures of 457 and 443 K on heating and cooling, respectively. Under ultraviolet irradiation, a clear yellowish-green emission peaked at 556 nm was observed for (R-3AQ)KI3. The calculated electronic structure shows that (R-3AQ)KI3 possesses a typical direct bandgap with a value of 3.74 eV and its valence band maximum and conduction band minimum primarily arise from the I-5p and I-5s orbitals, respectively. In addition, the elastic calculations indicate that (R-3AQ)KI3 displays a relatively large structure stiffness, relatively small elastic anisotropy, and fairly low acoustic velocity, owing to the rigid K–I bonds and the strong hydrogen bond interactions between the [KI3]2− perovskite framework and R-3AQ2+ cations. These results suggest that the mechanical robustness of this multifunctional (R-3AQ)KI3 makes it a good candidate material for sensing applications. [ABSTRACT FROM AUTHOR]

With the improvement of medical technology, the quality of life and prognosis of patients with malignant tumors have been greatly improved, and surgical treatment strategies for patients with spinal metastatic tumors have received extensive attention. Traditional open surgery for spinal metastases has problems such as large trauma, slow recovery, and influence on subsequent systemic treatment. Minimally invasive spine surgery has similar clinical outcomes to traditional open surgery, but minimally invasive spine surgery is less invasive and has a shorter recovery time. Minimally invasive spine surgery was initially applied to non-neoplastic diseases such as spinal degeneration and trauma, and was gradually applied to the treatment of spinal metastatic tumors and spinal deformities. For patients with spinal metastases, a shorter recovery time is helpful for early postoperative radiotherapy, thereby achieving a more satisfactory tumor control effect. This review discusses the application of minimally invasive spine surgery in the treatment of spinal metastatic tumors from the concept, surgical purpose, indications, and surgical selection, so as to provide reference for clinical practice. [ABSTRACT FROM AUTHOR]

Hyccin/FAM126A mutations are linked to hypomyelination and congenital cataract disease (HCC), but whether and how Hyccin/FAM126A deficiency causes hypomyelination remains undetermined. This study shows Hyccin/FAM126A expression was necessary for the expression of other components of the PI4KIIIα complex in Drosophila. Knockdown of Hyccin/FAM126A in glia reduced the enrichment of glial cells, disrupted axonal sheaths and visual ability in the visual system, and these defects could be fully rescued by overexpressing either human FAM126A or FAM126B, and partially rescued by overexpressing a plasma membrane-targeting recombinant mouse PI4KIIIα. Additionally, PI4KIIIα knockdown in glia phenocopied Hyccin/FAM126A knockdown, and this was partially rescued by overexpressing the recombinant PI4KIIIα, but not human FAM126A or FAM126B. This study establishes an animal model of HCC and indicates that Hyccin/FAM126A plays an essential role in glial enrichment and axonal sheath in a cell-autonomous manner in the visual system via controlling the expression and stabilization of the PI4KIIIα complex at the plasma membrane. • Hyccin/FAM126A expression is necessary for the expression of other components of the PI4KIIIα complex at the plasma membrane. • Hyccin/FAM126A plays an essential role in the glial enrichment and axonal sheath in a cell-autonomous manner in the visual system, via controlling the expression and stabilization of the PI4KIIIα complex at the plasma membrane. • This study successfully establishes the first animal model of HCC that replicates hypomyelination observed in HCC patients. [ABSTRACT FROM AUTHOR]

Few studies have examined the association of serum selenium with anemia‐related indicators and risk of anemia. We conducted a cross‐sectional analysis of 2,902 adults in 2003–2004 National Health and Nutrition Examination Survey database. Multivariable linear and logistic regression models were used to examine the association of serum selenium with anemia‐related indicators and risk of anemia. The nonlinear relationship was analyzed using a generalized additive model with the smoothing plot. A total of 1,472 males and 1,430 females with a mean age of 61.94 ± 13.73 years were included. Compared with the lowest quintile, the highest quintile of serum selenium was associated with increased level of serum iron (β = 12.44, 95% confidence interval [CI]: 7.14, 17.75, p <.001), mean corpuscular hemoglobin concentration (MCHC) (β = 0.14, 95%CI: 0.02, 0.26, p =.020), and hemoglobin (β = 0.40, 95%CI: 0.19, 0.61, p <.001), and decreased risk of anemia (odds ratio [OR] = 0.47, 95%CI: 0.28, 0.77, p =.002). Furthermore, smoothed plots suggested the nonlinear relationships between serum selenium and MCHC, hemoglobin level, and risk of anemia. Interestingly, on the left of inflection point, serum selenium was associated with decreased risk of anemia (OR = 0.972, 95%CI: 0.960, 0.985, p <.001), and then, the risk of anemia increased with increasing serum selenium concentration (OR = 1.011, 95%CI: 1.002, 1.021, p =.023). Future large‐scale, polycentric prospective studies should be conducted to verify our results. [ABSTRACT FROM AUTHOR]

Purpose: Collectin subfamily member 10 (COLEC10) encodes for collectin liver 1 (CL-L1), which is highly expressed in normal liver. Nevertheless, the association between COLEC10 and the prognosis of patients with hepatocellular carcinoma (HCC) remains unclear. To address this question, the prognostic value of COLEC10 expression in HCC was explored in this study. Patients and methods: Data from The Cancer Genome Atlas were used to compared transcriptional levels of COLEC10 in HCC samples and samples from healthy controls. In addition, COLEC10 mRNA and protein expression levels were analyzed in HCC tissue samples from Chinese patients and matched adjacent nontumorous tissue samples, by quantitative reverse-transcription polymerase chain reaction and immunohistochemistry, respectively. The prognostic value of COLEC10 was further examined using the Gene Expression Profiling Interactive Analysis online tool. Results: Both the mRNA and protein levels of COLEC10 were found to be downregulated in HCC tissues compared with normal controls. Survival analysis indicated that decreased mRNA and protein levels of COLEC10 were related with shorter overall survival in patients with HCC. In addition, univariate and multivariate analysis demonstrated that COLEC10 is an independent prognostic factor for overall survival of HCC patients. Conclusion: Together, the results suggest that decreased expression of COLEC10 may predict poor overall survival in patients with HCC. [ABSTRACT FROM AUTHOR]

Neuronal amyloid-β (Aβ) accumulation plays an important role in the pathogenesis of Alzheimer's disease (AD). The conformation and toxicity of Aβ are regulated by lipids on the plasma membrane. Previously, we found downregulation of Rolling Blackout (RBO) or phosphatidylinositol-4-kinase type IIIα (PI4KIIIα) reduces neuronal Aβ accumulation and associated neural deficits in a Drosophila model expressing Aβ42. In mammals, the homologs of RBO and PI4KIIIα were reported to form a plasma membrane-localized complex with a scaffold protein TTC7 and cytosolic protein Hyccin/FAM126A to tightly control the plasmalemmal level of phosphatidylinositol-4-phosphate. Here, we show genetic downregulation of Drosophila TTC7 and Hyccin also reduces neuronal Aβ accumulation and associated synaptic and motor defects as well as premature death in Aβ42-expressing flies, while overexpression of TTC7 and Hyccin produced the opposite effect. These results, together with our previous study, demonstrate that RBO/TTC7/PI4KIIIα/Hyccin regulate neuronal Aβ accumulation and associated neural deficits in the Drosophila model, further supporting the RBO/Efr3-PI4KIIIα complex as a potential therapeutic target for AD. [ABSTRACT FROM AUTHOR]

Abstract: A label‐free, highly sensitive and specific fluorescent sensor was developed for the detection of Ag+, biothiols and acetylcholinesterase (AChE) activity and for the screening of AChE inhibitors. The sensing approach was based on the conformational switch of human telomeric G‐rich sequence. The present assay was capable of detecting Ag+ in the range of 0 to 6.0 μM, with a detection limit of 34 nM. In addition, the proposed method was developed as a turn‐on cysteine‐sensing system, which presented a good response to cysteine in the range of 0 to 4.5 μM, and the detection limit was 25 nM. The cysteine‐sensing system could be used to detect the activity of AChE as low as 0.05 U/L in the range of 0.05 to 1.3 U/L. The proposed sensor was also promising in screening of AChE inhibitors. Furthermore, this method has been applied successfully to the sensing of Ag+ in tap water and lake water with satisfactory recovery. [ABSTRACT FROM AUTHOR]

The optimal therapy for advanced thymic carcinoma has long been controversial. Despite that complete (R0) resection is recommend as the first-line treatment, multidisciplinary approach including chemotherapy and radiotherapy should be considered for patients who lost the operation chance or received incomplete resection. Here, we present a case who received concurrent chemoradiotherapy (CCRT) after cytoreductive surgery. A complete response was observed and the patient has remained disease free for over 4 years. To our knowledge, this is the first report to demonstrate the efficacy of CCRT with cisplatin plus etoposide after incomplete surgery for advanced thymic carcinoma. [ABSTRACT FROM AUTHOR]

[Display omitted] Malignant brain tumors, a heterogeneous group of primary and metastatic neoplasms in the central nervous system (CNS), are notorious for their highly invasive and devastating characteristics, dismal prognosis and low survival rate. Recently, near-infrared (NIR) optical imaging modalities including fluorescence imaging (FLI) and photoacoustic imaging (PAI) have displayed bright prospect in innovation of brain tumor diagnoses, due to their merits, like noninvasiveness, high spatiotemporal resolution, good sensitivity and large penetration depth. Importantly, these imaging techniques have been widely used to vividly guide diverse brain tumor therapies in a real-time manner with high accuracy and efficiency. Herein, we provide a systematic summary of the state-of-the-art NIR contrast agents (CAs) for brain tumors single-modal imaging (e.g. , FLI and PAI), dual-modal imaging (e.g. , FLI/PAI, FLI/magnetic resonance imaging (MRI) and PAI/MRI) and triple-modal imaging (e.g. , MRI/FLI/PAI and MRI/PAI/computed tomography (CT) imaging). In addition, we update the most recent progress on the NIR optical imaging-guided therapies, like single-modal (e.g. , photothermal therapy (PTT), chemotherapy, surgery, photodynamic therapy (PDT), gene therapy and gas therapy), dual-modal (e.g. , PTT/chemotherapy, PTT/surgery, PTT/PDT, PDT/chemotherapy, PTT/chemodynamic therapy (CDT) and PTT/gene therapy) and triple-modal (e.g. , PTT/PDT/chemotherapy, PTT/PDT/surgery, PTT/PDT/gene therapy and PTT/gene/chemotherapy). Finally, we discuss the opportunities and challenges of the CAs and nanotheranostics for future clinic translation. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is extremely malignant and difficult to treat. The adenoviral early region 2 binding factors (E2Fs) target pathway is thought to have a major role in tumor growth. This study aimed to identify a predictive E2F target signature and facilitate individualized treatment for HCC patients. Methods: We constructed an E2F target-related gene profile using univariate COX and LASSO regression models and proved its predictive efficacy in external cohorts. Furthermore, we characterized the role of the E2F target pathway in pathway enrichment, immune cell infiltration, and drug sensitivity of HCC. Results: Lasso Cox regression created an E2F target-related gene signature of GHR, TRIP13, and CDCA8. HCC patients with high risk were correlated with shorter survival time, immune evasion, tumor stem cell characteristics and high sensitivity to Tipifarnib and Camptothecin drugs. Conclusion: Hepatocellular carcinoma prognosis was predicted by an E2F target signature. This finding establishes the theoretical usefulness of the E2F target route in customized identification and treatment for future research., 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 Zhang, Chang, Wang and Xu.)

Background: Currently, the prognosis and survival rate for patients bearing non-small cell lung cancer (NSCLC) is still quite poor, mainly due to lack of efficient theranostic paradigms to exert in time diagnostics and therapeutics. Methods: Herein, for NSCLC treatment, we offer a customized theranostic paradigm, termed NIR-IIb fluorescence diagnosis and synergistic surgery/starvation/chemodynamic therapeutics, with a newly designed theranostic nanoplatform PEG/MnCuDCNPs@GOx. The nanoplatform is composed of brightly NIR-II emissive downconversion nanoparticles (DCNPs)-core and Mn/Cu-silica shell loaded with glucose oxidase (GOx) to achieve synergistic starvation and chemodynamic therapy (CDT). Results: It is found that 10% Ce 3+ doped in the core and 100% Yb 3+ doped in the middle shell greatly improves the NIR-IIb emission up to even 20.3 times as compared to the core-shell DCNPs without Ce 3+ doping and middle shell. The bright NIR-IIb emission of the nanoplatform contributes to sensitive margin delineation of early-stage NSCLC (diameter < 1 mm) with a signal-to-background ratio (SBR) of 2.18, and further assists in visualizing drug distribution and guiding surgery/starvation/chemodynamic therapy. Notably, the starvation therapy mediated by GOx-driven oxidation reaction efficiently depletes intratumoral glucose, and supplies H 2 O 2 to boost the CDT mediated by the Mn 2+ and Cu 2+ , which consequently realized a highly effective synergistic treatment for NSCLC. Conclusion: This research demonstrates an efficient treatment paradigm for NSCLC with NIR-IIb fluorescence diganosis and image-guided synergistic surgery/starvation/chemodynamic therapeutics., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Water lettuce (Pistia stratiotes L.), is one of the emerging invasive weeds for inland water bodies in Asia and become a major problem for local water ecosystem. Biocontrol of water lettuce by mycobiota is being considered as a promising and sustainable method (Kongjornrak et al. 2019). During July 2021, a leaf blight of water lettuce was observed within about 1.5 ha in Shenxi stream (N25°66', E119°05') in Putian, Fujian, China. The disease severity was about 100% with 80% incidence, early symptoms appeared as small irregularly yellow or brown blight, severely infected leaves turned to be rot, then death and sink. Small pieces (5 × 5 mm) of symptomatic leaves were excised and surface disinfected with 75% ethanol and 0.1% HgCl2 solution, air dried and plated on potato dextrose agar (PDA). 3~5 days after incubation at 28°C, six fungal pure cultures showing similar morphology were obtained from the infected leaves. On PDA, colonies were flat, aerial mycelium grew sparsely, most of it grew inside the agar medium, it reverses white to grey to black with age. Hyphae were branched, septate, smooth and hyaline. Conidiophores mostly reduced to conidiogenous cells and setae were not observed. Conidiogenous cells were monoblastic, discrete and solitary, at first hyaline, subspherical, then turning to pale brown, ampulliform, 4.5-10 × 3.5-6 μm in size. Conidia were solitary, globose or ellipsoidal, black, smooth, some of it formed directly from the mycelia, aseptate, 8-12 μm diam (n=10). Genomic DNA was extracted from one of the representative isolate Z1. ITS1/ITS4 (Mills et al. 1992), Bt-2a/Bt-2b (Glass and Donaldson 1995) and EF1-728F/EF-2 (O'Donnell et al. 1998) primer pairs were used to amplify the isolate's internal transcribed spacer (ITS), the Beta-tubulin fragment (TUB) and the partial translation elongation factor (TEF1), respectively. The isolate's sequences were deposited in the GenBank with accession numbers of OM279539 (ITS), OM296034 (TUB) and OM296035 (TEF1). Phylogenetic analysis using maximum likelihood based on the ITS-TUB-TEF1 concatenated sequences from Nigrospora species revealed that isolate Z1 is closely clustered with N. osmanthi strain LC4487. The fungus was identified as N. osmanthi based on the morphological characteristics and molecular analyses (Hao et al. 2020; Wang et al. 2017). Pathogenicity test were performed using twenty inoculated and control plants, respectively. Conidial suspensions (107 CFU/ml) of Z1 isolate were spray-inoculated on the leaves of healthy water lettuce seedlings, while sterile distilled water was used as control. Inoculated and control plants were kept in the differential 50-liter plastic tanks and maintained in a greenhouse at room temperature (19 to 24°C) for one month. Symptoms appeared 7 days post inoculation, which was similar to what occurs in the field. No symptoms occurred on controls. Pathogen was reisolated and confirmed by morphology and molecular analysis. Koch's postulates were conducted twice. N. osmanthi is a pathogenic fungus of many crop plants, such as buckwheat (Shen et al 2021), Java tea (Ismail et al. 2022) or buffalograss (Mei et al. 2019) in Asia and particularly in China. However, to our knowledge, this is the first report of N. osmanthi causing leaf blight on water lettuce. Further studies on how to apply formulated N. osmanthi will be required so that the strain could be effectively used to control water lettuce, moreover, its environmental safety also need a rigorous experimental evaluation.

Background: Prone position ventilation (PPV) has been recommended for patients with acute respiratory distress syndrome (ARDS) to improve oxygenation. However, whether prolonged prone ventilation will aggravate hyperoxia and whether abdominal compression will aggravate permissive hypercapnia acidosis are topics of concern. We carried out a retrospective analysis to investigate the issues above., Methods: Clinical data were collected from 97 moderate-to-severe ARDS patients who received PPV as part of their treatment in the intensive care unit (ICU) of the First Affiliated Hospital of Guangzhou Medical University from November 2015 to May 2021. We collected arterial blood gas of patients according to the 3 periods: supine position ventilation (SPV), PPV early stage (within 4 hours), and PPV middle and late stage (6 hours or later). We established a linear mixed-effects models with "body position changes, times of PPV, gender, age, baseline SOFA, and baseline APACHE II" as fixed effects, and individual and the number of prone positions as random intercept and random slope to investigate the effect of body position changes on blood gas analysis., Results: Among the 97 patients received PPV included, 51 were ICU survivors. Arterial partial pressure of oxygen (PaO 2 ) and PaO 2 /fraction of inspired oxygen (FiO 2 ) ratio were significantly higher at the early, middle and late stages of PPV than those in SPV [PFR (mmHg): 158 (118.00, 203.00) vs. 161 (129.00, 202.75) vs. 123 (91.75, 163.00), P<0.05]. Despite the synchronized reduction of FiO 2 , the incidence of hyperoxia in the prone position was still significantly higher than that in the supine position [hyperoxia (%):33.33 vs . 33.56 vs . 12.42, P<0.05]; there was no significant change in arterial carbon dioxide partial pressure (PaCO 2 ) at each stage of PPV, but there was a significant increase in PH at PPV middle and late stages than those at early stage [PH: 7.39 (7.34, 7.42) vs. 7.37 (7.31, 7.41), P<0.05]., Conclusions: Although PPV improves the patients' oxygenation, the associated incidence of hyperoxia exceeds 33%. Down-regulate FiO 2 more sharply after PPV is necessary, if oxygenation conditions permit. PPV may alleviate the acidosis associated with permissive hypercapnia in ARDS patients treated with lung protective ventilation strategy (LPVS)., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-5907/coif). The authors have no conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

Background: Endometriosis (EM) is a common gynecological disorder that often leads to irregular menstruation and infertility. The pathogenesis of EM remains unclear and delays in diagnosis are common. Thus, it is urgent to explore potential biomarkers and underlying molecular mechanisms for EM diagnosis and therapies., Methods: Three EM-related datasets (GSE11691, GSE25628, and GSE86534) were downloaded from the Gene Expression Omnibus (GEO) which were integrated into a combined dataset after removing batch effect. Differentially expressed immune cell-related genes were obtained by CIBERSORT, WGCNA, and the identification of differentially expressed genes. Random forest model (RF), support vector machine model (SVM), and generalized linear model (GLM) were then constructed and the biomarkers for EM were determined. A nomogram evaluating the risk of disease was constructed and the validity was assessed by the calibration curve, DCA curve, and clinical impact curve. Single-gene Gene Set Enrichment Analysis (GSEA)was performed to explore the molecular mechanisms of biomarkers. The ceRNA regulatory network of biomarkers was created by Cytoscape and potential target drugs were obtained in the DGIdb database (Drug-Gene Interaction database).The expression levels of biomarkers from clinical samples was quantified by RT-qPCR., Results: The ratio of eight immune cells was significantly different between the eutopic and ectopic endometrium samples. A total of eight differentially expressed immune cell-related genes were investigated. The SVM model was a relatively suitable model for the prediction of EM and five genes (CXCL12, PDGFRL, AGTR1, PTGER3, and S1PR1) were selected from the model as biomarkers. The calibration curve, DCA curve, and clinical impact curve indicated that the nomogram based on the five biomarkers had a robust ability to predict disease. Single gene GSEA result suggested that all five biomarkers were involved in labyrinthine layer morphogenesis and transmembrane transport-related biological processes in EM. A ceRNA regulatory network containing 184 nodes and 251 edges was constructed. Seven drugs targeting CXCL12, 49 drugs targeting AGTR1, 16 drugs targeting PTGER3, and 21 drugs targeting S1PR1 were extracted as potential drugs for EM therapy. Finally, the expression of PDGFRL and S1PR1 in clinical samples was validated by RT-qPCR, which was consistent with the result of public database., Conclusions: In summary, we identified five biomarkers (CXCL12, PDGFRL, AGTR1, PTGER3, and S1PR1) and constructed diagnostic model, furthermore predicted the potential therapeutic drugs for EM. Collectively, these findings provide new insights into EM diagnosis and treatment., 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 © 2022 Jiang, Zhang, Wu, Zhang, Wei, Li, Huang, Chen and He.)

Background: Pyroptosis, a newly discovered type of programmed cell death, has both anti-tumor and tumor-promoting effects on carcinogenesis. In hepatocellular carcinoma (HCC), however, the associations between pyroptosis-regulated genes and prognosis, immune microenvironment, and immunotherapy response remain unclear. Samples and methods: Sequencing data were collected from The Cancer Genome Atlas database, The International Cancer Genome Consortium (ICGC), and The Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB). First, we investigated the expression levels and copy number variations (CNVs) of 56 pyroptosis genes in HCC and pan-cancer. Next, we identified 614 genes related to 56 pyroptosis-associated genes at the expression, mutation, and CNVs levels. Pathway enrichment analysis of 614 genes in the Hallmark, KEGG, and Reactome databases yielded a total of 253 significant signaling pathways. The pyroptosis-regulated genes (PRGs) comprised 108 genes that were derived from the top 20 signaling pathways, of which 57 genes had prognostic value in HCC. The least absolute shrinkage and selection operator (LASSO) analysis was performed to screen for PRGs with prognostic values. Ultimately, we constructed a risk score model with seven PRGs to predict HCC prognosis and validated its predictive value in three independent HCC cohorts. Risk scores were used to illustrate receiver operating characteristic (ROC) curves predicting 1, 3, and 5-years overall survival (OS). Single-sample gene set enrichment analysis (ssGSEA), was performed to study 28 types of immune cells infiltrated in HCC. The relationship between the risk signature and six immune checkpoint genes and immunotherapy was analyzed. Results: A total of seven PRGs were obtained following multiple screening steps. The risk score model containing seven PRGs was found to correlate significantly with the HCC prognosis of the training group. In addition, we validated the risk score model in two additional HCC cohorts. The risk score significantly correlated with infiltrating immune cells (i. e. CD4 + T cells, etc.), ICB key molecules (i. e. HAVCR2, etc.), and ICB response. Conclusions: This study demonstrated a vital role of PRGs in predicting the prognosis and immunotherapy response of HCC patients. The risk model could pave the way for drugs targeting pyroptosis and immune checkpoints in HCC., 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 © 2022 Zhang and Wang.)

Background: The presence of alveolar epithelial type II cells (AECIIs) is one of the most important causes of bronchopulmonary dysplasia (BPD). Exosomes from bone mesenchymal stem cells (BMSCs) can reduce hyperoxia-induced damage and provide better results in terms of alveolar and pulmonary vascularization parameters than BMSCs. Currently, intervention studies using BMSC-derived exosomes on the signaling pathways regulating proliferation and apoptosis of alveolar epithelial cells under the condition of BPD have not been reported. This study investigated the effects of rat BMSC-derived exosomes on the proliferation and apoptosis of hyperoxia-induced primary AECIIs in vitro ., Methods: The isolated AECIIs were grouped as follows: normal control (21% oxygen), hyperoxia (85% oxygen), hyperoxia+exosome (20 µg/mL), hyperoxia+exosome+LY294002 (PI3K/Akt inhibitor, 20 µM), and hyperoxia+exosome+rapamycin (mTOR inhibitor, 5 nM). We used the PI3K/Akt inhibitor LY294002 and the mTOR inhibitor rapamycin to determine the roles of the PI3K/Akt and mTOR signaling pathways. The effects of BMSC-derived exosomes on AECII proliferation and apoptosis were assessed, respectively., Results: Decreased levels of the antiapoptotic protein Bcl-2, the cell proliferation protein Ki67, p-PI3K, p-Akt, and p-mTOR, as well as increased levels of AECII apoptosis and the proapoptotic protein Bax in the hyperoxia group were observed. Notably, Sprague Dawley rat BMSC-derived exosomes could reverse the effect of hyperoxia on AECII proliferation. However, the application of LY294002 and rapamycin inhibited the protective effects of BMSC-derived exosomes., Conclusion: Our findings revealed that BMSC-derived exosomes could regulate the expression of apoptosis-related proteins likely via the PI3K/Akt/mTOR signaling pathway, thereby preventing hyperoxia-induced AECII apoptosis., Competing Interests: The authors declare there are no competing interests., (©2022 Yang et al.)

Background: Patients with moderate to severe acute respiratory distress syndrome (ARDS) have been recommended to receive prone position ventilation (PPV). However, the dynamic changes in respiratory mechanics during PPV and their relationship with the prognosis have not been sufficiently evaluated. In addition, the impact of using neuromuscular blocking agents (NMBAs) during PPV on respiratory mechanics is not clear enough. Thus, the study aims to investigate the above-mentioned issues., Methods: A prospective cohort study was conducted on 22 patients with moderate to severe ARDS who received PPV in the intensive care unit (ICU) of the First Affiliated Hospital of Guangzhou Medical University. A multifunctional gastric tube was used to measure the patients' respiratory mechanics during supine position ventilation (SPV), early PPV (PPV within 4 h of initiation), and middle/late PPV (more than 6 h after the initiation of PPV). Longitudinal data were analyzed with generalized estimating equations (GEE)., Results: Compared with SPV, the esophageal pressure swings (ΔPes) measured during the PPV was significantly higher (SPV 7.46 vs. early PPV 8.00 vs. middle/late PPV 8.30 cmH 2 O respectively; P SPV vs. middle/late PPV =0.025<0.05). A stratified analysis by patients' outcome showed that the peak airway pressure (Ppeak), ΔPes and respiration rate (RR) in the death group were significantly higher than survival group. On the contrary, the tidal volume (Vt), diaphragmatic electromyogram (EMGdi) and PaO 2 /FiO 2 ratio (PFR) in the death group were significantly lower than survival group. Notably, the ΔPes and transpulmonary driving pressure (DPL) were significantly lower in the patients treated with NMBAs (7.08 vs. 8.76 cmH 2 O ΔPes; P<0.01), (14.82 vs. 18.08 cmH 2 O DPL; P<0.001)., Conclusions: During the transition from SPV to early PPV and then to middle/late PPV, the ΔPes in the PPV were greater than SPV and it fluctuated within a normal range while oxygenation improved significantly in all patients. The Ppeak, ΔPes and RR in the death group were significantly higher than survival group. When NMBAs were used, the ΔPes, inspiratory transpulmonary pressure (PLei), driving pressure (DP) and DPL were significantly decreased, suggesting that the rational combination of NMBAs and PPV may exert a synergistic protective effect on the lungs., 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-22-291/coif). The authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Background: Interferon (IFN) is widely used in clinical practice and nebulization inhalation is one of the commonly used routes of administration. However, nebulization drugs such as interferon-α (IFN-α) with large molecular weights may deposit in the membrane of the breathing filters, causing its resistance to gradually increase. Thus, our study explores the effect of IFN-α and other nebulization drugs on the resistance of breathing circuit filters under invasive mechanical ventilation., Methods: We divided 96 breathing filters into eight groups. The baseline group was not treated while the blank group was installed but were not nebulized. The remaining groups received jet nebulized or vibrating nebulized with either normal saline, Combivent, Amphotericin B, or IFN-α at a frequency of once every 12 hours separately and were removed from the breathing circuit after 24 hours. The resistance of the filter of each group was then measured and statistical comparisons were made., Results: Filter resistance of the IFN-α jet nebulization group was greater than that of the other groups, and there were statistical differences except for the Amphotericin B jet nebulization group. Comparison of the resistance [cmH 2 O/(L·s)] of the IFN-α jet nebulization group vs . the baseline group showed 2.56 (2.40, 2.68) vs . 2.26 (2.03, 2.40), P=0.037; of the IFN-α jet nebulization group vs . the blank group showed 2.56 (2.40, 2.68) vs . 2.11 (1.98, 2.27), P=0.003; of the IFN-α jet nebulization group vs . the normal saline group: 2.56 (2.40, 2.68) vs . 2.16 (2.08, 2.32), P=0.023; of the IFN-α jet nebulization group vs . the Combivent jet nebulization group: 2.56 (2.40, 2.68) vs . 2.18 (2.14, 2.27), P=0.018; and of the IFN-α jet nebulization group vs . the Amphotericin B jet nebulization group: 2.56 (2.40, 2.68) vs . 2.33 (2.05, 2.45), P=0.221. The effect of jet nebulization and vibrating mesh nebulization on the resistance of breathing filters showed no significant statistical difference., Conclusions: Jet nebulization with IFN-α significantly increased the resistance of the breathing filter within 24 hours and there was no significant difference in filter resistance between jet nebulization and vibrating mesh nebulization of IFN-α or Amphotericin B., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-84/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: The nuclear division cycle 80 (NDC80) complex assures proper chromosome segregation during the cell cycle progression. SPC25 is a crucial component of NDC80, and its role in hepatocellular carcinoma (HCC) has been explored recently. This study characterized the differential expression of SPC25 in HCC patients of different races and HBV infection status., Methods: Expression patterns of SPC25 were evaluated in TCGA and Chinese HCC patients. Kaplan-Meier analysis was applied to examine the predictive value of SPC25. In vitro and in vivo functional assays were conducted to explore the role of SPC25 in HCC. Bioinformatics methods were applied to investigate the regulatory mechanisms of SPC25., Findings: The mRNA levels of SPC25 were up-regulated in HCC. SPC25 has a significantly higher transcriptional level in Asian patients than Caucasian patients. SPC25 promoted HCC cell proliferation in vitro and tumor growth in vivo by accelerating the cell cycle. We identified transcription factors, miRNAs, and immune cells that may interact with SPC25., Interpretation: The findings suggest that increased expression of SPC25 is associated with poor prognosis of HCC and enhances the proliferative capacity of HCC cells. SPC25 could serve as a valuable prognostic marker and a novel treatment target for HCC.

Beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) is crucial for the degradation of IκBα. Our previous transcriptome sequencing analysis revealed that tetraspanin 15 (TSPAN15) was significantly upregulated in clinical oesophageal squamous cell carcinoma (OSCC) tissues. Here, we show that high TSPAN15 expression in OSCC tissues is significantly associated with lymph node and distant metastasis, advanced clinical stage, and poor prognosis. Elevated TSPAN15 expression is, in part, caused by the reduction of miR-339-5p. Functional studies demonstrate that TSPAN15 promotes metastatic capabilities of OSCC cells. We further show that TSPAN15 specifically interacts with BTRC to promote the ubiquitination and proteasomal degradation of p-IκBα, and thereby triggers NF-κB nuclear translocation and subsequent activation of transcription of several metastasis-related genes, including ICAM1, VCAM1, uPA, MMP9, TNFα, and CCL2. Collectively, our findings indicate that TSPAN15 may serve as a new biomarker and/or provide a novel therapeutic target to OSCC patients.

Background: Family with sequence similarity 3, member C (FAM3C) has been identified as a novel regulator in epithelial-mesenchymal transition (EMT) and metastatic progression. However, the role of FAM3C in esophageal squamous cell carcinoma (ESCC) remains unexplored. The purpose of present study is to illustrate the role of FAM3C in predicting outcomes of patients with ESCC., Methods: FAM3C expression was measured in ESCC tissues and the matched adjacent nontumorous tissues by quantitative real-time RT-PCR and Western blot analysis. The relationship between FAM3C expression and prognosis of ESCC patients was further evaluated by univariate and multivariate regression analyses. Univariate and multivariate analyses of the prognostic factors were performed using Cox proportional hazards model., Results: The FAM3C mRNA expression was remarkably upregulated in ESCC compared with their nontumor counterparts (P < 0.001). In addition, high expression of FAM3C was significantly associated with pT stage (P = 0.014) , pN stage (P = 0.026) and TNM stage (P = 0.003). Kaplan-Meier analysis showed that the 7-year overall survival rate in the group with high expression of FAM3C was poorer than that in low expression group (32.0 versus 70.9 %; P < 0.001). Univariate and multivariate analyses demonstrated that FAM3C was an independent risk factor for overall survival. Moreover, Stratified analysis revealed that FAM3C expression could differentiate the prognosis of patients in early clinical stage (TNM stage I-II)., Conclusions: FAM3C expression was dramatically increased in ESCC and might serve as a valuable prognostic indicator for ESCC patients after surgery.

Background: Inositol-1,4,5-trisphosphate-3-kinase-A (ITPKA) has recently been found to be implicated in the tumor progression of various cancers. However, the expression and the prognostic value of ITPKA in hepatocellular carcinoma (HCC) remains unexplored. The aim of this study is to investigate the clinical significance of ITPKA expression in HCC., Methods: We determined the expression level of ITPKA in 135 cases of HCC tissues and the matched adjacent nontumorous tissues by quantitative real-time RT-PCR. The correlation between ITPKA expression and prognosis of HCC patients was further evaluated by univariate and multivariate analysis. Multivariate analysis of the prognostic factors was performed with Cox proportional hazards model., Results: Up-regulation of ITPKA occurred in 48.9% of primary HCCs compared with their nontumor counterparts (P < 0.001). In addition, high expression of ITPKA was significantly associated with vascular invasion (P = 0.001) and TNM stage (P = 0.005). Kaplan-Meier analysis showed that the 5-year overall survival (OS) and relapse-free survival (RFS) rate in the group with high expression of ITPKA is poorer than that in low expression group (32.2 and 26.8% versus 59.2 and 57.7%). Univariate and multivariate analyses revealed that ITPKA was an independent prognostic factor for OS and RFS. Moreover, Stratified analysis revealed that its prognostic significance still existed within the subgroup of patients with early clinical stage (TNM stage I) or normal serum AFP level (≤25 μg/L)., Conclusion: Our data indicated that ITPKA expression was significantly up-regulated in HCC and could serve as a potential novel prognostic biomarker for HCC patients after surgery.