Correction of Presbyopia by Monocular Bi-Aspheric Ablation Profile.

The study aims to evaluate visual acuity and objective visual quality before and after the monocular bi-aspheric ablation profile for correction of presbyopia surgery. This prospective self-control study included 20 cases and 38 eyes of patients who underwent monocular bi-aspheric ablation profile correction of myopia with presbyopia at the Eye Hospital of Shandong University of Traditional Chinese Medicine from January 2023 to January 2024. These patients were selected for observation, and each patient's preoperative and postoperative uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), corrected distance visual acuity (CDVA), spherical aberration (SA) (within 6 mm), horizontal and vertical coma (within 6 mm), and corneal aspheric index (Q-value) (within 6 mm) were evaluated. Statistical data analysis was performed at different time points before and after the operation. There were statistically significant differences in UDVA between dominant and non-dominant eyes before and after surgery (Z = -3.784, p < 0.001; Z = -3.817, p < 0.001). Post-operatively, 90% of the non-dominant eyes achieved UNVA of J1 and above, and 95% of the bilateral eyes achieved UNVA of J1 and above. Significant differences were found in the SA of the dominant eyes, which showed a positive increase (Z= -3.784, p < 0.001); however, compared with the dominant eye, the SA of the non-dominant eye was negatively increased, but the difference was not statistically significant (p = 0.08). There was a significant difference in the vertical coma of the dominant eye before and after the operation, but there was no significant difference in non-dominant eyes. There was no significant difference in the change of binocular horizontal coma before and after the operation. There were significant changes in the Q value of both eyes before and after the operation (Z = -3.923, p < 0.001; Z = -3.51, p < 0.001). After the monocular bi-aspheric ablation profile, the cornea of the non-dominant eye showed a prolate shape, negative SA increased, and the UDVA and UNVA improved after the operation.

Bismuth-based mesoporous nanoball carrying sorafenib for synergistic photothermal and molecularly-targeted therapy in an orthotopic hepatocellular carcinoma xenograft mouse model.

Sorafenib (SOR), a multi-kinase inhibitor for advanced hepatocellular carcinoma (HCC), has limited clinical application due to severe side effects and drug resistance. To overcome these challenges, we developed a bismuth-based nanomaterial (BOS) for thermal injury-assisted continuous targeted therapy in HCC. Initially, the mesoporous nanomaterial was loaded with SOR, forming the BOS@SOR nano-carrier system for drug delivery and controlled release. Notably, compared to targeted or photothermal therapy alone, the combination therapy using this nano-carrier system significantly impaired cell proliferation and increased apoptosis. In vivo efficacy evaluations demonstrated that BOS@SOR exhibited excellent biocompatibility, confirmed through hemolysis and biochemical analyses. Additionally, BOS@SOR enhanced contrast in computed tomography, aiding in the precise identification of HCC size and location. The photothermal therapeutic properties of bismuth further contributed to the synergistic anti-tumor activity of BOS@SOR, significantly reducing tumor growth in an orthotopic xenograft HCC model. Taken together, encapsulating SOR within a bismuth-based mesoporous nanomaterial creates a multifunctional and environmentally stable nanocomposite (BOS@SOR), enhancing the therapeutic effect of SOR and presenting an effective strategy for HCC treatment.

Aberrant cytoplasmic expression of UHRF1 restrains the MHC-I-mediated anti-tumor immune response.

Immunotherapy successfully complements traditional cancer treatment. However, primary and acquired resistance might limit efficacy. Reduced antigen presentation by MHC-I has been identified as potential resistance factor. Here we show that the epigenetic regulator ubiquitin-like with PHD and ring finger domains 1 (UHRF1), exhibits altered expression and aberrant cytosolic localization in cancerous tissues, where it promotes MHC-I ubiquitination and degradation. Cytoplasmic translocation of UHRF1 is induced by its phosphorylation on a specific serine in response to signals provided by factors present in the tumor microenvironment (TME), such as TGF-ß, enabling UHRF1 to bind MHC-I. Downregulation of MHC-I results in suppression of the antigen presentation pathway to establish an immune hostile TME. UHRF1 inactivation by genetic deletion synergizes with immune checkpoint blockade (ICB) treatment and induces an anti-tumour memory response by evoking low-affinity T cells. Our study adds to the understanding of UHRF1 in cancer immune evasion and provides a potential target to synergize with immunotherapy and overcome immunotherapeutic resistance.

The potential role of iron-carbon micro-electrolysis materials in curtailing lag-phase stimulates kitchen waste anaerobic digestion at different solid contents: Performance, synergistic effect and microbial response.

High-solid anaerobic digestion (HSAD) of kitchen waste was generally faced to the common problems such as systemic acidification, prolonged lag-phase time and low methane production. Iron-carbon micro-electrolysis (ICME) materials exhibited advantages that porous structure, large specific surface area and excellent conductivity. It was beneficial for organic compounds to hydrolysis. Moreover, ICME materials could establish direct interspecies electron transfer (DIET) pathway between bacteria and methanogens. ICME materials were commonly used to enhance the AD of wastewater, but they were rarely applied to HSAD of kitchen waste. In this study, ICME materials were utilized to enhance HSAD of kitchen waste at different solid content conditions. The results showed that the highest cumulative biogas yield (705.23 mL/g VS) was obtained in the experimental group (TS = 10%), which was 94.15% higher than that of the control group. At the same time, the addiction of ICME could shorten lag-phase time. Electrochemical characteristics and XPS analysis showed that ICME materials promoted the release of Fe2+ in the AD system and acceleration of direct interspecies electron transfer between microorganisms. Microbial community analysis showed that ICME materials enriched electroactive bacteria (Proteiniphilum), Methanosarcina, Methanobrevibacter and Methanofollis. Functional gene prediction revealed that ICME materials increased the relative abundance of carbohydrate transport and metabolism and coenzyme transport and metabolism. It provided a potential measure to treat kitchen waste.

Recent advances in copper homeostasis-involved tumor theranostics.

As the third essential trace element in the human body, copper plays a crucial role in various physiological processes, which lays the foundation for its broad applications in cancer treatments. The overview of copper, including pharmacokinetics, signaling pathways, and homeostasis dysregulation, is hereby discussed. Additionally, cuproptosis, as a newly proposed cell death mechanism associated with copper accumulation, is analyzed and further developed for efficient cancer treatment. Different forms of Cu-based nanoparticles and their advantages, as well as limiting factors, are introduced. Moreover, the unique characteristics of Cu-based nanoparticles give rise to their applications in various imaging modalities. In addition, Cu-based nanomaterials are featured by their excellent photothermal property and ROS-associated tumor-killing potential, which are widely explored in diverse cancer therapies and combined therapies. Reducing the concentration of Cu2+/Cu+ is another cancer-killing method, and chelators can meet this need. More importantly, challenges and future prospects are identified for further research.

Cost-effectiveness of pembrolizumab plus chemotherapy vs. chemotherapy as first-line treatment for advanced biliary tract cancer in China and the US.

Background: Pembrolizumab is a potentially valuable treatment. However, patients, doctors, and healthcare decision-makers are uncertain about its cost-effectiveness and an appropriate pricing for this new therapy. This study aims to appraise the cost-effectiveness of pembrolizumab as a first-line treatment for advanced biliary tract cancer (BTC) patients in China and the United States (US). Methods: A Markov model was constructed from the perspectives of healthcare systems in both China and the US for pharmacoeconomic evaluation. Patient baseline characteristics and key clinical data were sourced from the KEYNOTE-966 trial (ClinicalTrials.gov, NCT04003636). Costs and utilities were collected from drug cost websites and published literature. Cumulative costs (in USD), life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were measured and compared. Price simulations were conducted under given willingness-to-pay (WTP) thresholds to provide pricing scheme references. The model's robustness was analyzed through one-way sensitivity analysis and probabilistic sensitivity analysis. Results: Basic data analysis illustrates that pembrolizumab ($2662.41/100 mg) in combination with chemotherapy regimen was not cost-effective relative to chemotherapy regimens at the WTP threshold of $38,201.19 in China, and the additional cost relative to chemotherapy regimens was $77,114.94 (ICER $556,689.47/QALY) while increasing 0.14 QALYs. Pembrolizumab ($54.71/1 mg) also increased efficacy by 0.14 QALYs in the US, but remained also not cost-effective at the US WTP threshold of $229,044, and the total cost increased by $160,425.24 (ICER $1,109,462.92/QALY). Conclusion: Compared with chemotherapy, pembrolizumab plus chemotherapy reduces the disease of burden. However, at its current price, it may not be a cost-effective treatment for advanced BTC in both China and the US. This study can aid decision-makers in making optimal choices.

TIMP-1 Promotes Expression of MCP-1 and Macrophage Migration by Inducing Fli-1 in Experimental Liver Fibrosis.

Background and Aims: Tissue inhibitor of metalloproteinase-1 (TIMP-1) plays a role in the excessive generation of extracellular matrix in liver fibrosis. This study aimed to explore the pathways through which TIMP-1 controls monocyte chemoattractant protein-1 (MCP-1) expression and promotes hepatic macrophage recruitment. Methods: Liver fibrosis was triggered through carbon tetrachloride, and an adeno-associated virus containing small interfering RNA targeting TIMP-1 (siRNA-TIMP-1) was administered to both rats and mice. We assessed the extent of fibrosis and macrophage recruitment. The molecular mechanisms regulating macrophage recruitment by TIMP-1 were investigated through transwell migration assays, luciferase reporter assays, the use of pharmacological modulators, and an analysis of extracellular vesicles (EVs). Results: siRNA-TIMP-1 alleviated carbon tetrachloride-induced liver fibrosis, reducing macrophage migration and MCP-1 expression. Co-culturing macrophages with hepatic stellate cells (HSCs) post-TIMP-1 downregulation inhibited macrophage migration. In siRNA-TIMP-1-treated HSCs, microRNA-145 (miRNA-145) expression increased, while the expression of Friend leukemia virus integration-1 (Fli-1) and MCP-1 was inhibited. Downregulation of Fli-1 led to decreased MCP-1 expression, whereas Fli-1 overexpression increased MCP-1 expression within HSCs. Transfection with miRNA-145 mimics reduced the expression of both Fli-1 and MCP-1, while miRNA-145 inhibitors elevated the expression of both Fli-1 and MCP-1 in HSCs. miRNA-145 bound directly to the 3'-UTR of Fli-1, and miRNA-145-enriched EVs secreted by HSCs after TIMP-1 downregulation influenced macrophage recruitment. Conclusions: TIMP-1 induces Fli-1 expression through miRNA-145, subsequently increasing MCP-1 expression and macrophage recruitment. MiRNA-145-enriched EVs from HSCs can transmit biological information and magnify the function of TIMP-1.

Early changes in corneal densitometry after FS-LASIK combined with accelerated corneal cross-linking for correction of high myopia.

AIM: To observe the effects of femtosecond laser-assisted excimer laser in situ keratomileusis combined with accelerated corneal cross-linking (FS-LASIK Xtra) on corneal densitometry after correcting for high myopia. METHODS: In this prospectively study, 130 patients underwent FS-LASIK or FS-LASIK Xtra for high myopia. Their right eyes were selected for inclusion in the study, of which 65 cases of 65 eyes in the FS-LASIK group, 65 patients with 65 eyes in the FS-LASIK Xtra group. Patients were evaluated for corneal densitometry at 1, 3, and 6mo postoperatively using Pentacam Scheimpflug imaging. RESULTS: Preoperative differences in corneal densitometry between the FS-LASIK and FS-LASIK Xtra groups in different ranges were not statistically significant (P>0.05). Layer-by-layer analysis revealed statistically significant differences in the anterior (120 µm), central, and total layer corneal densitometry between the FS-LASIK and FS-LASIK Xtra groups at 1 and 3mo postoperatively (all P<0.05), the FS-LASIK Xtra group is higher than that of the FS-LASIK group. Analysis of different diameter ranges showed statistically significant differences between the FS-LASIK group and the FS-LASIK Xtra group at 1mo postoperatively in the ranges of 0-2, 2-6, and 6-10 mm (both P<0.05); At 3mo postoperatively, the FS-LASIK Xtra group is higher than that of the FS-LASIK group in the ranges of 0-2 and 2-6 mm (P<0.05). At 6mo postoperatively, there were no statistically significant differences in corneal densitometry between the FS-LASIK group and the FS-LASIK Xtra group in different diameter ranges (all P>0.05). CONCLUSION: There is an increase in internal corneal densitometry during the early postoperative period after FS-LASIK Xtra for correction of high myopia. However, the densitometry values decreased to the level of conventional FS-LASIK at 6mo after surgery, with the most significant changes observed in the superficial central zone.

Tartaric acid ameliorates experimental non-alcoholic fatty liver disease by activating the AMP-activated protein kinase signaling pathway.

Tartaric acid (TA) has been shown beneficial effects on blood pressure and lipid levels. However, its effect on non-alcoholic fatty liver disease (NAFLD) remains unknown. This study aimed to investigate the role of TA in experimental NAFLD. Mice were fed a Western diet for 8 weeks, followed by administration of TA or a vehicle for an additional 12 weeks while continuing on the Western diet. Blood biochemistry including transaminases and glucose tolerance test and liver tissue RNA sequencing (RNA-seq), lipid content, and histology were investigated. The HepG2 cell line was used to explore the mechanism by which TA regulates lipid metabolism. We found that TA significantly improved weight gain, insulin resistance, hepatic steatosis, inflammation and fibrosis in Western diet-fed mice. By comparing gene expression differences, we found that TA affects pathways related to lipid metabolism, inflammatory response, and fibrosis. Furthermore, TA effectively reduced oleic acid-induced lipid accumulation in HepG2 cells and downregulated the genes associated with fatty acid synthesis, which were enriched in the AMP-activated protein kinase (AMPK) signaling pathway. TA also enhanced the phosphorylation of AMPK which could be reverted by the AMPK inhibitor Compound C in HepG2 cells. Our study suggests that TA improves experimental NAFLD by activating the AMPK signaling pathway. These findings indicate that TA may serve as a potential therapy for the human NAFLD.

Ethylene controls three-dimensional growth involving reduced auxin levels in the moss Physcomitrium patens.

The conquest of land by plants was concomitant with, and possibly enabled by, the evolution of three-dimensional (3D) growth. The moss Physcomitrium patens provides a model system for elucidating molecular mechanisms in the initiation of 3D growth. Here, we investigate whether the phytohormone ethylene, which is believed to have been a signal before land plant emergence, plays a role in 3D growth regulation in P. patens. We report ethylene controls 3D gametophore formation, based on results from exogenously applied ethylene and genetic manipulation of PpEIN2, which is a central component in the ethylene signaling pathway. Overexpression (OE) of PpEIN2 activates ethylene responses and leads to earlier formation of gametophores with fewer gametophores produced thereafter, phenocopying ethylene-treated wild-type. Conversely, Ppein2 knockout mutants, which are ethylene insensitive, show initially delayed gametophore formation with more gametophores produced later. Furthermore, pharmacological and biochemical analyses reveal auxin levels are decreased in the OE lines but increased in the knockout mutants. Our results suggest that evolutionarily, ethylene and auxin molecular networks were recruited to build the plant body plan in ancestral land plants. This might have played a role in enabling ancient plants to acclimate to the continental surfaces of the planet.

Chromatin Remodeling in Patient-Derived Colorectal Cancer Models.

Patient-Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient-derived models of cancer (PDMC). Nevertheless, how patient tumor cells evolve in these models and the impact on drug response remains unclear. Herein, the transcriptomic and chromatin accessibility landscapes of matched colorectal cancer (CRC) PDO, PDX, PDO-derived PDX (PDOX), and original patient tumors (PT) are compared. Two major remodeling axes are discovered. The first axis delineates PDMC from PT, and the second axis distinguishes PDX and PDO. PDOX are more similar to PDX than PDO, indicating the growth environment is a driving force for chromatin adaptation. Transcription factors (TF) that differentially bind to open chromatins between matched PDO and PDOX are identified. Among them, KLF14 and EGR2 footprints are enriched in PDOX relative to matched PDO, and silencing of KLF14 or EGR2 promoted tumor growth. Furthermore, EPHA4, a shared downstream target gene of KLF14 and EGR2, altered tumor sensitivity to MEK inhibitor treatment. Altogether, patient-derived CRC cells undergo both common and distinct chromatin remodeling in PDO and PDX/PDOX, driven largely by their respective microenvironments, which results in differences in growth and drug sensitivity and needs to be taken into consideration when interpreting their ability to predict clinical outcome.

Bacterial heat shock protein: A new crosstalk between T lymphocyte and macrophage via JAK2/STAT1 pathway in bloodstream infection.

Bloodstream infection (BSI) refers to the infection of blood by pathogens. Severe immune response to BSI can lead to sepsis, a systemic infection leading to multiple organ dysfunction, coupled with drug resistance, mortality, and limited clinical treatment options. This work aims to further investigate the new interplay between bacterial exocrine regulatory protein and host immune cells in the context of highly drug-resistant malignant BSI. Whether interfering with related regulatory signaling pathways can reverse the inflammatory disorder of immune cells. In-depth analysis of single-cell sequencing results in Septic patients for potential immunodeficiency factors. Analysis of key proteins enriched by host cells and key pathways using proteomics. Cell models and animal models validate the pathological effects of DnaK on T cells, MAITs, macrophages, and osteoclasts. The blood of patients was analyzed for the immunosuppression of T cells and MAITs. We identified that S. maltophilia-DnaK was enriched in immunodeficient T cells. The activation of the JAK2/STAT1 axis initiated the exhaustion of T cells. Septic patients with Gram-negative bacterial infections exhibited deficiencies in MAITs, which correspond to IFN-γ. Cellular and animal experiments confirmed that DnaK could facilitate MAIT depletion and M1 polarization of macrophages. Additionally, Fludarabine mitigated M1 polarization of blood, liver, and spleen in mice. Interestingly, DnaK also repressed osteoclastogenesis of macrophages stimulated by RANKL. S.maltophilia-DnaK prompts the activation of the JAK2/STAT1 axis in T cells and the M1 polarization of macrophages. Targeting the DnaK's crosstalk can be a potentially effective approach for treating the inflammatory disorder in the broad-spectrum drug-resistant BSI.

Breaking NGF-TrkA immunosuppression in melanoma sensitizes immunotherapy for durable memory T cell protection.

Melanoma cells, deriving from neuroectodermal melanocytes, may exploit the nervous system's immune privilege for growth. Here we show that nerve growth factor (NGF) has both melanoma cell intrinsic and extrinsic immunosuppressive functions. Autocrine NGF engages tropomyosin receptor kinase A (TrkA) on melanoma cells to desensitize interferon γ signaling, leading to T and natural killer cell exclusion. In effector T cells that upregulate surface TrkA expression upon T cell receptor activation, paracrine NGF dampens T cell receptor signaling and effector function. Inhibiting NGF, either through genetic modification or with the tropomyosin receptor kinase inhibitor larotrectinib, renders melanomas susceptible to immune checkpoint blockade therapy and fosters long-term immunity by activating memory T cells with low affinity. These results identify the NGF-TrkA axis as an important suppressor of anti-tumor immunity and suggest larotrectinib might be repurposed for immune sensitization. Moreover, by enlisting low-affinity T cells, anti-NGF reduces acquired resistance to immune checkpoint blockade and prevents melanoma recurrence.

Impact of CT-guided hookwire localization on tumor spread through air spaces in stage IA lung adenocarcinoma.

Background: It remains undetermined whether preoperative computed tomography (CT)-guided hookwire localization would result in elevated risk of tumor spread through air spaces (STAS) in stage IA lung adenocarcinoma. Methods: A total of 1836 patients who underwent lobectomy were included. To eliminate the potential impact of confounding factors on producing STAS, propensity score-matching (PSM) was used to create two balanced subgroups stratified by implementation of hookwire localization. We also introduced an external cohort including 1486 patients to explore the effect of hookwire localization on the incidence of STAS and patient survival after sublobar resection (SR). For proactive simulation of hookwire localization, 20 consecutive lobectomy specimens of p-stage IA lung adenocarcinoma were selected. Results: Ex vivo tests revealed that mechanical artifacts presenting as spreading through a localizer surface (STALS) could be induced by hookwire localization but be distinguished by CD68 and AE1/3 antibody-based immunohistochemistry. The distance of STALS dissemination tended to be shorter compared with real STAS (P = 0.000). After PSM, implementation of hookwire localization was not associated with elevated STAS incidence, nor worse survival in p-stage IA patients undergoing lobectomy irrespective of STAS. Conclusions: CT-guided hookwire localization might induce mechanical artifacts presenting as STALS which could be distinguished by immunohistochemistry, but would not affect survival in p-stage IA disease. Surgeons can be less apprehensive about performing hookwire localization in relation to STAS on stage IA disease suitable for SR.

Feasibility study of intubation in lateral position using Viva-sight double-lumen tube combined with video laryngoscope in patients undergoing pulmonary lobectomy.

BACKGROUND: Double-lumen tube (DLT) intubation in lateral decubitus position is rarely reported. We designed this study to evaluate the feasibility of VivaSight double-lumen tube (VDLT) intubation assisted by video laryngoscope in lateral decubitus patients. METHODS: Patients undergoing elective video-assisted thoracoscopic surgery (VATS) for lung lobectomy were assessed for eligibility between January 2022 and December, 2022. Eligible patients were randomly allocated into supine intubation group (group S) and lateral intubation group (group L) by a computer-generated table of random numbers. The prime objective was to observe whether the success rate of VDLT intubation in lateral position with the aid of video laryngoscope was not inferior to that in supine position. RESULTS: A total of 116 patients were assessed, and 88 eligible patients were randomly divided into group L (n = 44) and group S (n = 44). The success rate of the first attempt intubation in the L group was 90.5%, lower than that of S group (97.7%), but there was no statistical difference (p > 0.05). Patients in both groups were intubated with VDLT for no more than 2 attempts. The mean intubation time was 91.98 ± 26.70 s in L group, and 81.39 ± 34.35 s in S group (p > 0.05). The incidence of the capsular malposition in the group L was 4.8%, less than 36.4% of group S (p < 0.001). After 24 h of follow-up, it showed a higher incidence of sore throat in group S, compared to that in group L (p = 0.009). CONCLUSION: Our study shows the comprehensive success rate of intubation in lateral decubitus position with VDLT assisted by video laryngoscope is not inferior to that in supine position, with less risk of intraoperative tube malposition and postoperative sore throat. TRIAL REGISTRATION: Chinese Clinical Trail Register (ChiCTR2200062989).

ATR inhibition induces synthetic lethality in mismatch repair-deficient cells and augments immunotherapy.

The mismatch repair (MMR) deficiency of cancer cells drives mutagenesis and offers a useful biomarker for immunotherapy. However, many MMR-deficient (MMR-d) tumors do not respond to immunotherapy, highlighting the need for alternative approaches to target MMR-d cancer cells. Here, we show that inhibition of the ATR kinase preferentially kills MMR-d cancer cells. Mechanistically, ATR inhibitor (ATRi) imposes synthetic lethality on MMR-d cells by inducing DNA damage in a replication- and MUS81 nuclease-dependent manner. The DNA damage induced by ATRi is colocalized with both MSH2 and PCNA, suggesting that it arises from DNA structures recognized by MMR proteins during replication. In syngeneic mouse models, ATRi effectively reduces the growth of MMR-d tumors. Interestingly, the antitumor effects of ATRi are partially due to CD8+ T cells. In MMR-d cells, ATRi stimulates the accumulation of nascent DNA fragments in the cytoplasm, activating the cGAS-mediated interferon response. The combination of ATRi and anti-PD-1 antibody reduces the growth of MMR-d tumors more efficiently than ATRi or anti-PD-1 alone, showing the ability of ATRi to augment the immunotherapy of MMR-d tumors. Thus, ATRi selectively targets MMR-d tumor cells by inducing synthetic lethality and enhancing antitumor immunity, providing a promising strategy to complement and augment MMR deficiency-guided immunotherapy.

Landscape analysis and overview of the literature on oxidative stress and pulmonary diseases.

Oxidative stress is caused by an imbalance in oxidant/antioxidant processes and is a critical process in pulmonary diseases. As no truly effective therapies exist for lung cancer, lung fibrosis and chronic obstructive pulmonary disease (COPD), at present, it is important to comprehensively study the relationship between oxidative stress and pulmonary diseases to identify truly effective therapeutics. Since there is no quantitative and qualitative bibliometric analysis of the literature in this area, this review provides an in-depth analysis of publications related to oxidative stress and pulmonary diseases over four periods, including from 1953 to 2007, 2008 to 2012, 2013 to 2017, and 2018 to 2022. Interest in many pulmonary diseases has increased, and the mechanisms and therapeutic drugs for pulmonary diseases have been well analyzed. Lung injury, lung cancer, asthma, COPD and pneumonia are the 5 most studied pulmonary diseases related to oxidative stress. Inflammation, apoptosis, nuclear factor erythroid 2 like 2 (NRF2), mitochondria, and nuclear factor-κB (NF-κB) are rapidly becoming the most commonly used top keywords. The top thirty medicines most studied for treating different pulmonary diseases were summarized. Antioxidants, especially those targeting reactive oxygen species (ROS) in specific organelles and certain diseases, may be a substantial and necessary choice in combined therapies rather than acting as a single "magic bullet" for the effective treatment of refractory pulmonary diseases.

Clinical implications and molecular features of tertiary lymphoid structures in stage I lung adenocarcinoma.

AIMS: We investigated the clinical implications and molecular features of TLS in stage I lung adenocarcinoma (LUAD). METHODS: We retrospectively reviewed the clinicopathological characteristics of 540 patients with p-stage I LUAD. Logistic regression analysis was applied to determining the relationships between clinicopathological features and the presence of TLS. TLS-associated immune infiltration pattern and signature genes were characterized using the transcriptomic profiles of 511 LUADs from The Cancer Genome Atlas (TCGA) database. RESULTS: The presence of TLS was associated with a higher pT stage, low- and middle-grade patterns, and the absence of tumor spreading through air spaces (STAS) and subsolid nodules. Multivariate Cox regression analysis identified that the presence of TLS was associated with favorable overall survival (OS) (p < 0.001) and recurrence-free survival (RFS) (p < 0.001). Subgroup analysis showed that the most favorable OS (p < 0.001) and RFS (p < 0.001) favored the TLS + PD-1- subgroup. The presence of TLS was characterized by abundance in antitumor immunocytes including activated CD8+ T and B cells as well as dentritic cells in TCGA cohort. CONCLUSION: The presence of TLS was an independent favorable factor for patients with stage I LUAD. The presence TLS was featured by special immune profiles which might aid oncologists in determining personalized adjuvant treatment.

Microbial response behavior to powdered activated carbon in high-solids anaerobic digestion of kitchen waste: Metabolism and functional prediction analysis.

Anaerobic digestion (AD) can not only treat organic waste, but also recycle energy. However, high-solids AD of kitchen waste usually failed due to excessive acidification. In this study, the effect of activated carbon (AC) on kitchen waste AD performance was investigated under high-solids conditions (total solids contents = 15%). The results showed that efficiencies of acidogenesis and methanogenesis were promoted in presence of moderate concentration (50 g/L > AC >5 g/L), but high concentration (AC >70 g/L) weakened AD performance. Moreover, AC addition enhanced the methane production rate from 66.0 mL/g VS to 231.50 mL/g VS, i.e., up to 250.7%. High-throughput sequencing results demonstrated that the abundance of electroactive DMER64 increased from less than 1%-29.7% (20 g/L AC). As AC gradually increased，aceticlastic methanogenesis changed to hydrogenotrophic pathway. Predicted functional analysis indicated that AC can enhance abundances of energy and inorganic ion metabolism, resulting in high methane production.

Diagnostic and economic value of carcinoembryonic antigen, carbohydrate antigen 19-9, and carbohydrate antigen 72-4 in gastrointestinal cancers.

BACKGROUND: The diagnostic and economic value of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and CA72-4 for gastrointestinal malignant tumors lacked evaluation in a larger scale. AIM: To reassess the diagnostic and economic value of the three tumor biomarkers. METHODS: A retrospective analysis of all 32857 subjects who underwent CEA, CA19-9, CA72-4, gastroscopy and colonoscopy from October 2006 to May 2018 was conducted. Then, we assessed the discrimination and clinical usefulness. Total cost, cost per capita and cost-effectiveness ratios were used to evaluate the economic value of two schemes (gastrointestinal endoscopy for all people without blood tests vs both gastroscopy and colonoscopy when blood tests were positive). RESULTS: The analysis of 32857 subjects showed that CEA was a qualified biomarker for colorectal cancer (CRC), while the diagnostic efficiencies of CA72-4 were catastrophic for all gastrointestinal cancers (GICs). Regarding early diagnosis, only CEA could be used for early CRC. The combination of biomarkers didn't greatly increase the area under the curve. The economic indicators of CEA were superior to those of CA19-9, CA72-4 and any combination. At the threshold of 1.8 µg/L to 10.4 µg/L, all four indicators of CEA were lower than those in the scheme that conducted gas-trointestinal endoscopy only. Subgroup analysis implied that the health checkup of CEA for people above 65 years old was economically valuable. CONCLUSION: CEA had qualified diagnostic value for CRC and superior economic value for GICs, especially for elderly health checkup subjects. CA72-4 was not suitable as a diagnostic biomarker.