GPR34-mediated sensing of lysophosphatidylserine released by apoptotic neutrophils activates type 3 innate lymphoid cells to mediate tissue repair.

Neutrophils migrate rapidly to damaged tissue and play critical roles in host defense and tissue homeostasis. Here we investigated the mechanisms whereby neutrophils participate in tissue repair. In an intestinal epithelia injury model, neutrophil depletion exacerbated colitis and associated with reduced interleukin (IL)-22 and limited activation of type 3 innate lymphoid cells (ILC3s). Co-culture with neutrophils activated ILC3s in a manner dependent on neutrophil apoptosis. Metabolomic analyses revealed that lysophosphatidylserine (LysoPS) from apoptotic neutrophils directly stimulated ILC3 activation. ILC3-specific deletion of Gpr34, encoding the LysoPS receptor GPR34, or inhibition of downstream PI3K-AKT or ERK suppressed IL-22 production in response to apoptotic neutrophils. Gpr34-/- mice exhibited compromised ILC3 activation and tissue repair during colon injury, and neutrophil depletion abrogated these defects. GPR34 deficiency in ILC3s limited IL-22 production and tissue repair in vivo in settings of colon and skin injury. Thus, GPR34 is an ILC3-expressed damage-sensing receptor that triggers tissue repair upon recognition of dying neutrophils.

The entry of unclosed autophagosomes into vacuoles and its physiological relevance.

It is widely stated in the literature that closed mature autophagosomes (APs) fuse with lysosomes/vacuoles during macroautophagy/autophagy. Previously, we showed that unclosed APs accumulated as clusters outside vacuoles in Vps21/Rab5 and ESCRT mutants after a short period of nitrogen starvation. However, the fate of such unclosed APs remains unclear. In this study, we used a combination of cellular and biochemical approaches to show that unclosed double-membrane APs entered vacuoles and formed unclosed single-membrane autophagic bodies after prolonged nitrogen starvation or rapamycin treatment. Vacuolar hydrolases, vacuolar transport chaperon (VTC) proteins, Ypt7, and Vam3 were all involved in the entry of unclosed double-membrane APs into vacuoles in Vps21-mutant cells. Overexpression of the vacuolar hydrolases, Pep4 or Prb1, or depletion of most VTC proteins promoted the entry of unclosed APs into vacuoles in Vps21-mutant cells, whereas depletion of Pep4 and/or Prb1 delayed the entry into vacuoles. In contrast to the complete infertility of diploid cells of typical autophagy mutants, diploid cells of Vps21 mutant progressed through meiosis to sporulation, benefiting from the entry of unclosed APs into vacuoles after prolonged nitrogen starvation. Overall, these data represent a new observation that unclosed double-membrane APs can enter vacuoles after prolonged autophagy induction, most likely as a survival strategy.

Scene-based dual domain non-uniformity correction algorithm for stripe and optics-caused fixed pattern noise removal.

Non-uniformity is a long-standing problem that significantly degrades infrared images through fixed pattern noise (FPN). Existing scene-based algorithms for non-uniformity correction (NUC) effectively eliminate stripe FPN assuming consistent inter-frame non-uniformity. However, they are ineffective in handling spatially continuous optical FPN. In this paper, a scene-based dual domain correction approach is proposed to address the non-uniformity problem by simultaneously removing stripe and optics-caused FPN. We achieve this through gain correction in the frequency domain and offset correction in the spatial domain. To remove stripes, we approximate the desired image using a guided filter and iteratively update the bias correction parameters frame by frame. For optics-caused noise removal, we separate low frequency noise from the scene using Fourier transform and update the gain correction parameters accordingly. To mitigate ghost artifacts, a combined strategy is introduced to adaptively adjusts learning rates and weights during the updating stage. Comprehensive evaluations demonstrate that our proposed approach outperforms compared methods in both real and simulated non-uniformity infrared videos.

A Single Amino Acid Residue Defines the Difference in NLRP3 Inflammasome Activation between NEK7 and NEK6.

The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a critical component of the innate immune system that is activated by microbial infections and cellular stress signals. The molecular mechanism of NLRP3 inflammasome activation remains not fully understood. As an NLRP3-interacting partner, NEK7 has emerged as a critical mediator for NLRP3 inflammasome activation. In contrast to NEK7, NEK6, the closely related member of the NEK family, does not support NLRP3 inflammasome activation. In this study, we show that the mouse NEK7 catalytic domain, which shares high sequence identity with the counterpart of NEK6, mediates its interaction with NLRP3 and inflammasome activation in mouse macrophages. Within their catalytic domains, a single amino acid residue at a corresponding position (R121NEK7, Q132NEK6) differentiates their function in NLRP3 inflammasome activation. Surprisingly, substitution of the glutamine residue to an arginine residue at position 132 confers NEK6 the ability of NLRP3 binding and inflammasome activation in mouse macrophages. Furthermore, our results suggest a structural pocket surrounding the residue R121 of NEK7 that is essential for NLRP3 binding and inflammasome activation.

First-principles studies on the electronic and contact properties of monolayer Ga2STe-metal contacts.

Monolayer (ML) Janus III-VI compounds have attracted the use of multiple competitive platforms for future-generation functional electronics, including non-volatile memories, field effect transistors, and sensors. In this work, the electronic and interfacial properties of ML Ga2STe-metal (Au, Ag, Cu, and Al) contacts are systematically investigated using first-principles calculations combined with the non-equilibrium Green's function method. The ML Ga2STe-Au/Ag/Al contacts exhibit weak electronic orbital hybridization at the interface, while the ML Ga2STe-Cu contact exhibits strong electronic orbital hybridization. The Te surface is more conducive to electron injection than the S surface in ML Ga2STe-metal contact. Quantum transport calculations revealed that when the Te side of the ML Ga2STe is in contact with Au, Ag and Cu electrodes, p-type Schottky contacts are formed. When in contact with the Al electrode, an n-type Schottky contact is formed with an electron SBH of 0.079 eV. When the S side of ML Ga2STe is in contact with Au and Al electrodes, p-type Schottky contacts are formed, and when it is in contact with Ag and Cu electrodes, n-type Schottky contacts are formed. Our study will guide the selection of appropriate metal electrodes for constructing ML Ga2STe devices.

Alcohol dehydrogenase 1 is a tubular mitophagy-dependent apoptosis inhibitor against septic acute kidney injury.

Alcohol dehydrogenase 1 (ADH1) is an alcohol-oxidizing enzyme with poorlydefined biology. Here we report that ADH1 is highly expressed in kidneys of mice with lethal endotoxemia and is transcriptionally upregulated in tubular cells by lipopolysaccharide (LPS) stimuli through TLR4/NF-κB cascade. The Adh1 knockout (Adh1KO) mice with lethal endotoxemia displayed increased susceptibility to acute kidney injury (AKI) but not systemic inflammatory response. Adh1KO mice develop more severe tubular cell apoptosis in comparison to Adh1 wild-type (Adh1WT) mice during course of lethal endotoxemia. ADH1 deficiency facilitates the LPS-induced tubular cell apoptosis in a caspase-dependent manner. Mechanistically, ADH1 deficiency dampens tubular mitophagy that relies on PINK1-Parkin pathway characterized by the reduced membrane potential, reactive oxygen species (ROS) and release of fragmented mtDNA to cytosol. Kidney-specific overexpression of PINK1 and Parkin by adeno-associated viral vector 9 (AAV9) delivery ameliorates AKI exacerbation in Adh1KO mice with lethal endotoxemia. Our study supports the notion that ADH1 is critical for blockade of tubular apoptosis mediated by mitophagy, allowing the rapid identification and targeting of alcohol-metabolic route applicable to septic AKI.

Indole-3-acetic acid regulating the initial adhesion of microalgae in biofilm formation.

Regulating the microalgal initial adhesion in biofilm formation is a key approach to address the challenges of attached microalgae cultivation. As a type of phytohormone, Indole-3-acetic acid (IAA) can promote the growth and metabolism of microalgae. However, limited knowledge has been acquired of how IAA can change the initial adhesion of microalgae in biofilm formation. This study focused on investigating the initial adhesion of microalgae under different IAA concentrations exposure in biofilm formation. The results showed that IAA showed obvious hormesis-like effects on the initial adhesion ability of microalgae biofilm. Under exposure to the low concentration (0.1 mg/L) of IAA, the initial adhesion quantity of microalgae on the surface of the carrier reached the highest value of 7.2 g/m2. However, exposure to the excessively high concentration (10 mg/L) of IAA led to a decrease in the initial adhesion capability of microalgal biofilms. The enhanced adhesion of microalgal biofilms due to IAA was attributed to the upregulation of genes related to the Calvin Cycle, which promoted the synthesis of hydrophobic amino acids, leading to increased protein secretion and altering the surface electron donor characteristics of microalgal biofilms. This, in turn, reduced the energy barrier between the carriers and microalgae. The research findings would provide crucial support for the application of IAA in regulating the operation of microalgal biofilm systems.

PDGFRß + cell HIF2α is dispensable for white adipose tissue metabolic remodeling and hepatic lipid accumulation in obese mice.

BACKGROUND: Obesity is associated with extensive white adipose tissue (WAT) expansion and remodeling. Healthy WAT expansion contributes to the maintenance of energy balance in the liver, thereby ameliorating obesity-related hepatic steatosis. Tissue-resident mesenchymal stromal cell populations, including PDGFRß + perivascular cells, are increasingly recognized pivotal as determinants of the manner in which WAT expands. However, the full array of regulatory factors controlling WAT stromal cell functions remains to be fully elucidated. Hypoxia-inducible factors (HIFs) are critical regulators in WAT stromal cell populations such as adipocyte precursor cells (APCs). It is revealed that HIF1α activation within PDGFRß + stromal cells results in the suppression of de novo adipogenesis and the promotion of a pro-fibrogenic cellular program in obese animals. However, the role of HIF2α in PDGFRß + cells remains undetermined in vivo. METHODS: New genetic models were employed in which HIF1α (encoded by the Hif1a gene) and HIF2α (encoded by the Epas1 gene) are selectively inactivated in PDGFRß + cells in an inducible manner using tamoxifen (TAM). With these models, both in vitro and in vivo functional analysis of PDGFRß + cells lacking HIF proteins were performed. Additionally, comprehensive metabolic phenotyping in diet-induced mouse models were performed to investigate the roles of PDGFRß + cell HIF proteins in WAT remodeling, liver energy balance and systemic metabolism. RESULTS: Unlike HIF1α inactivation, the new findings in this study suggest that inducible ablation of HIF2α in PDGFRß + cells does not cause apparent effects on WAT expansion induced by obesogenic diet. The adipogenic ability of PDGFRß + APCs is not significantly altered by genetic HIF2α ablation. Moreover, no difference of key parameters associated with healthy WAT remodeling such as improvements of WAT insulin sensitivity, reduction in metabolic inflammation, as well as changes in liver fat accumulation or systemic glucose metabolism, is detected in PDGFRß + cell Epas1-deficient mice. CONCLUSION: The new findings in this study support that, in contrast to HIF1α, PDGFRß + cell HIF2α appears dispensable for WAT metabolic remodeling and the resulting effects on liver metabolic homeostasis in diet-induced obesity, underscoring the isoform-specific roles of HIFα proteins in the regulation of adipose tissue biology.

The leucine-rich repeat (LRR) domain of NLRP3 is required for NLRP3 inflammasome activation in macrophages.

The NLRP3 inflammasome is a critical component of innate immunity that defends the host from microbial infections. However, its aberrant activation contributes to the pathogenesis of several inflammatory diseases. Activation of the NLRP3 inflammasome induces the secretion of proinflammatory cytokines IL-1ß and IL-18 and pyroptotic cell death. NLRP3 contains a leucine-rich repeat (LRR) domain at its C terminus. Although posttranslational modifications in this LRR domain have been shown to regulate NLRP3 inflammasome activation, the role of the entire LRR domain in NLRP3 inflammasome activation remains controversial. Here, we generated mouse macrophages that express an endogenous NLRP3 mutant lacking the LRR domain. Deletion of the LRR domain diminished NLRP3 inflammasome activation in macrophages. Furthermore, using NLRP3-deficient macrophages that are reconstituted with NLRP3 mutants lacking the LRR domain, we found that deletion of the LRR domain inhibited NLRP3 inflammasome activation. Mechanistically, deletion of the LRR domain inhibited NLRP3 self-association, oligomerization, and interaction with the essential regulator NEK7. Our results demonstrate a critical role for the LRR domain in NLRP3 inflammasome activation.

Two-way communication between the nucleus and mitochondria via a micropeptide in renal fibrosis.

Micropeptides are small proteins encoded by short open reading frames mostly located in long noncoding RNAs. Mitoregulin (MOXI) is a nuclear encoded micropeptide initially identified in the inner mitochondrial membrane to regulate fatty acid ß-oxidation. In this issue of Kidney International, Li et al. report that MOXI is upregulated in both human fibrotic kidneys and murine models of renal fibrosis. Remarkably, MOXI functions in the nucleus, where it forms a transcriptional complex with N-acetyltransferase 14 and c-Jun to facilitate the expression of fibrotic genes. By working in the nucleus and mitochondria, MOXI may channel the 2-way communication between these organelles, adding a new layer of complexity in the cell biology of renal fibrogenesis.

4-Octyl itaconate attenuates LPS-induced acute kidney injury by activating Nrf2 and inhibiting STAT3 signaling.

BACKGROUND: Septic acute kidney injury (S-AKI) is the leading form of acute kidney failure among hospitalized patients, and the inflammatory response is involved in this process. 4-octyl itaconate (4-OI) is a multi-target itaconate derivative with potent anti-inflammatory action. However, it remains elusive whether and how 4-OI contributes to the regulation of S-AKI. METHODS: We employed a lipopolysaccharide (LPS)-induced AKI murine model and explored the potential renoprotective effect of 4-OI in vivo. In vitro experiments, BUMPT cells, a murine renal tubular cell line, were conducted to examine the effects of 4-OI on inflammation, oxidative stress, and mitophagy. Moreover, STAT3 plasmid was transfected in BUMPT cells to investigate the role of STAT3 signaling in the 4-OI-administrated state. RESULTS: We demonstrate that 4-OI protects against S-AKI through suppressing inflammation and oxidative stress and enhancing mitophagy. 4-OI significantly reduced the levels of Scr, BUN, Ngal as well as the tubular injury in LPS-induced AKI mice. 4-OI restrained inflammation by reducing macrophage infiltration and suppressing the expression of IL-1ß and NLRP3 in the septic kidney. 4-OI also reduced ROS levels, as well as cleaved caspase-3 and boosted antioxidants such as HO-1, and NQO1 in mice. In addition, the 4-OI treatment significantly promoted mitophagy. Mechanistically, 4-OI activated Nrf2 signaling and suppressed phosphorylated STAT3 in vivo and vitro. Molecular docking revealed the binding affinity of 4-OI towards STAT3. ML385, a specific Nrf2 inhibitor, partially repressed the anti-inflammatory and anti-oxidative effects of 4-OI and partially restricted the mitophagy induced by 4-OI in vivo and in vitro. Transfected with STAT3 plasmid partially suppressed mitophagy and the anti-inflammatory effect provoked by 4-OI in vitro. CONCLUSION: These data suggest that 4-OI ameliorates LPS-induced AKI by suppressing inflammation and oxidative stress and enhancing mitophagy through the overactivation of the Nrf2 signaling pathway, and inactivation of STAT3. Our study identifies 4-OI as a promising pharmacologic for S-AKI.

Helicobacter macacae MazF interplays with Escherichia coli homologs and enhances antibiotic tolerance.

BACKGROUND: Toxin-antitoxin systems are highly variable, even among strains of the same bacterial species. The MazEF toxin-antitoxin system is found in many bacteria and plays important roles in various biological processes such as antibiotic tolerance and phage defense. However, no interplay of MazEF systems between different species was reported. MATERIALS AND METHODS: MazEF toxin-antitoxin system of Helicobacter macacae was examined in three Escherichia coli strains with and without endogenous MazEF knockout. In vivo toxicity, antibiotic tolerance, and live/dead staining followed by flowcytometry analysis were performed to evaluate the functionality and interplay of the toxin-antitoxin system between the two species. RESULTS: Controlled ectopic expression of MazF of H. macacae (MazFhm) in E. coli did not affect its growth. However, in endogenous MazEF knockout E. coli strains, MazFhm expression caused a sharp growth arrest. The toxicity of MazFhm could be neutralized by both the antitoxin of MazE homolog of H.macacae and the antitoxin of MazE of E. coli, indicating interplay of MazEF toxin-antitoxin systems between the two species. Induced expression of MazFhm enhanced tolerance to a lethal dose of levofloxacin, suggesting enhanced persister formation, which was further confirmed by live/dead cell staining. CONCLUSIONS: The MazEF toxin-antitoxin system of H. macace enhances persister formation and thus antibiotic tolerance in E. coli. Our findings reveal an interplay between the MazEF systems of H. macacae and E. coli, emphasizing the need to consider this interaction while evaluating the toxicity and functionality of MazF homologs from different species in future studies.

RBC Transfusion Strategy in Oncological Patients with Chronic RBC Transfusion Therapy.

BACKGROUND: Red blood cell (RBC) transfusion therapy has greatly reduced mortality and morbidity in multiply transfused patients with oncological malignancies. The aim of this study was to underline the necessity of introducing a policy for extended RBC phenotyping of these patients and for the issuing of antigen-matched blood (at least for E antigen). METHODS: Multivariate logistic regression analysis was used to evaluate the associations of age, gender, transfusion history, and various malignancies with the development of red cell alloimmunization. RESULTS: Given the results of antibody identification, we finally obtained 732 cases to be analyzed, designating them as the p group. The respiratory system (231/732; 31.6%), digestive system (273/732; 37.3%), and female reproductive system (127/732; 17.3%) had the three highest alloimmunization rates in the p group. We screened 81 cases from the p group for which antibody screening in our laboratory had historically yielded negative results. Among the 81 cases with antibody seroconversion, anti-E was the most frequently observed antibody (37%). CONCLUSIONS: The results related to multivariate logistic regression analysis of the Rh group indicate that, in contrast to the other variates, transfusion confers a strongly increased risk of Rh blood system-related red cell alloimmunization. To reduce alloimmunization in tumor patients, it will be essential to introduce a policy for extended RBC phenotyping of high-risk patients and for the issuing of antigen-matched blood (at least for E antigen).

Clinical features and prognosis of pregnancy-related renal damage and pregnancy after chronic kidney disease.

OBJECTIVE: To explore the clinical features of renal damage related to pregnancy and pregnancy after chronic kidney disease (CKD), providing clinical evidence for the relationship between renal damage and pregnancy. METHODS: A retrospective analysis was performed on patients admitted to our hospital between March 2013 and February 2021 who had both pregnancy and kidney damage. The study collected pathology results from renal biopsies, 24-hour urinary protein quantity, albumin (Alb), serum creatinine (Scr), blood lipids, coagulation function, blood routine, and other indicators during and after pregnancy. RESULTS: This study included 82 cases, with 48 cases in the pregnancy-related renal damage group. Thirty-four cases were in the post-CKD pregnancy group. Of the patients, 30 cases (88.24%) had CKD stage 1-2. Results showed better pregnancy and fetal outcomes in the post-CKD pregnancy group compared to the pregnancy-related renal damage group (Ρ was 0.029 and 0.036, respectively). Renal biopsy pathology revealed that 16 cases (33.33%) in the pregnancy-related renal damage group mainly had focal segmental glomerulosclerosis (FSGS), while the post-CKD pregnancy group was dominated by 14 cases (43.75%) of IgA nephropathy. The first blood test indicators revealed that the pregnancy-related renal damage group had lower estimated glomerular filtration (eGFR) and Alb levels compared to the post-CKD pregnancy group (Ρ was 0.003 and 0.000, respectively). Additionally, 24-hour urinary protein quantity, total cholesterol (Tch), triglyceride (TG), and platelet (PLT) counts were higher in the pregnancy-related renal damage group compared to the post-CKD pregnancy group (Ρ was 0.005, 0.001, 0.008, and 0.031, respectively). The abnormal rate of Scr during pregnancy was 41.67% (20/48) in the pregnancy-related renal damage group and 17.39% (4/23) in the post-CKD pregnancy group, with a statistically significant difference (Ρ was 0.043). CONCLUSION: The pregnancy-related renal damage group is mainly associated with FSGS, while the post-CKD pregnancy group is characterized by IgA nephropathy. Patients with CKD1-2 can have a successful pregnancy after achieving good control of eGFR, albumin, 24-hour urinary protein quantity and other indicators, resulting in better pregnancy and fetal outcomes. Abnormal Scr levels during pregnancy of pregnancy-related renal damage can be improved within 3 months after delivery.

TH-302-loaded nanodrug reshapes the hypoxic tumour microenvironment and enhances PD-1 blockade efficacy in gastric cancer.

BACKGROUND: Hypoxia, a common characteristic of the tumour microenvironment, is involved in tumour progression and immune evasion. Targeting the hypoxic microenvironment has been implicated as a promising antitumour therapeutic strategy. TH-302 can be selectively activated under hypoxic conditions. However, the effectiveness of TH-302 in gastric cancer combined immunotherapy remains unclear. METHODS: We designed mPEG-PLGA-encapsulated TH-302 (TH-302 NPs) to target the hypoxic area of tumour tissues. A particle size analyzer was used to measure the average size and zeta potential of TH-302 NPs. The morphology was observed by transmission electron microscopy and scanning electron microscopy. The hypoxic area of tumour tissues was examined by immunofluorescence assays using pimonidazole. Flow cytometry analysis was performed to measure the levels of TNF-α, IFN-γ, and granzyme B. The synergistic antitumour activity of the combination of TH-302 NPs with anti-PD-1 (α-PD-1) therapy was assessed in vitro and in vivo. Haematoxylin and eosin staining of major organs and biochemical indicator detection were performed to investigate the biological safety of TH-302 NPs in vivo. RESULTS: TH-302 NPs inhibited the proliferation and promoted the apoptosis of gastric cancer cells under hypoxic conditions. In vitro and in vivo experiments confirmed that TH-302 NPs could effectively alleviate tumour hypoxia. TH-302 NPs exhibited high bioavailability, effective tumour-targeting ability and satisfactory biosafety. Moreover, the combination of TH-302 NPs with α-PD-1 significantly improved immunotherapeutic efficacy in vivo. Mechanistically, TH-302 NPs reduced the expression of HIF-1α and PD-L1, facilitated the infiltration of CD8+ T cells and increased the levels of TNF-α, IFN-γ, and granzyme B in tumours, thereby enhancing the efficacy of α-PD-1 therapy. CONCLUSION: TH-302 NPs alleviated the hypoxic tumour microenvironment and enhanced the efficacy of PD-1 blockade. Our results provide evidence that TH-302 NPs can be used as a safe and effective nanodrug for combined immunotherapy in gastric cancer treatment.

Endoplasmic reticulum stress contributes to cisplatin-induced chronic kidney disease via the PERK-PKCδ pathway.

BACKGROUND: Cisplatin is an effective chemotherapeutic drug, but it may induce both acute and chronic kidney problems. The pathogenesis of chronic kidney disease (CKD) associated with cisplatin chemotherapy remains largely unclear. METHODS: Mice and renal tubular cells were subjected to repeated low-dose cisplatin (RLDC) treatment to induce CKD and related pathological changes. The roles of endoplasmic reticulum (ER) stress, PERK, and protein kinase C-δ (PKCδ) were determined using pharmacological inhibitors and genetic manipulation. RESULTS: ER stress was induced by RLDC in kidney tubular cells in both in vivo and in vitro models. ER stress inhibitors given immediately after RLDC attenuated kidney dysfunction, tubular atrophy, kidney fibrosis, and inflammation in mice. In cultured renal proximal tubular cells, inhibitors of ER stress or its signaling kinase PERK also suppressed RLDC-induced fibrotic changes and the expression of inflammatory cytokines. Interestingly, RLDC-induced PKCδ activation, which was blocked by ER stress or PERK inhibitors, suggesting PKCδ may act downstream of PERK. Indeed, suppression of PKCδ with a kinase-dead PKCδ (PKCδ-KD) or Pkcδ-shRNA attenuated RLDC-induced fibrotic and inflammatory changes. Moreover, the expression of active PKCδ-catalytic fragment (PKCδ-CF) diminished the beneficial effects of PERK inhibitor in RLDC-treated cells. Co-immunoprecipitation assay further suggested PERK binding to PKCδ. CONCLUSION: These results indicate that ER stress contributes to chronic kidney pathologies following cisplatin chemotherapy via the PERK-PKCδ pathway.

Development and External Validation of Machine Learning-Based Models for Predicting Lung Metastasis in Kidney Cancer: A Large Population-Based Study.

The accuracy of indices widely used to evaluate lung metastasis (LM) in patients with kidney cancer (KC) is insufficient. Therefore, we aimed at developing a model to estimate the risk of developing LM in KC based on a large population size and machine learning algorithms. Demographic and clinicopathologic variables of patients with KC diagnosed between 2004 and 2017 were retrospectively analyzed. We performed a univariate logistic regression analysis to identify risk factors for LM in patients with KC. Six machine learning (ML) classifiers were established and tuned using the ten-fold cross-validation method. External validation was performed using clinicopathologic information from 492 patients from the Southwest Hospital, Chongqing, China. Algorithm performance was estimated by analyzing the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, precision, recall, F1 score, clinical decision analysis (DCA), and clinical utility curve (CUC). A total of 52,714 eligible patients diagnosed with KC were enrolled, of whom 2,618 developed LM. Variables of age, sex, race, T stage, N stage, tumor size, histology, and grade were identified as important for the prediction of LM. The extreme gradient boosting (XGB) algorithm performed better than other models in both the internal validation (AUC: 0.913, sensitivity: 0.873, specificity: 0.809, and F1 score: 0.325) and the external validation (AUC: 0.904, sensitivity: 0.750, specificity: 0.878, and F1 score: 0.364). This study established a predictive model for LM in KC patients based on ML algorithms which showed high accuracy and applicative value. A web-based predictor was built using the XGB model to help clinicians make more rational and personalized decisions.

Effect of one-lung ventilation on the correlation between left and right cerebral saturation.

BACKGROUND: To investigate if the correlation between left and right cerebral tissue oxygen saturation (SctO2) was affected by one-lung ventilation (OLV) in patients undergoing lung cancer surgery. METHODS: Patients who underwent surgery for lung cancer were enrolled. Left and right SctO2 were collected during anesthesia. The primary outcome was the correlation between left and right SctO2 at 30 min after OLV which was analysed by Pearson correlation and linear regression model. Secondary outcomes included the trend of left-right SctO2 change over the first 30 min after OLV, correlation of left-right SctO2 during OLV for each patient; maximal difference between left-right SctO2 and its relationship with postoperative delirium. RESULTS: Left-right SctO2 was moderately correlated at baseline (r = 0.690, P < 0.001) and poorly correlated at 30 min after OLV (r = 0.383, P < 0.001) in the Pearson correlation analysis. Linear regression analysis showed a poor correlation between left and right SctO2 at 30 min after OLV (r = 0.323, P < 0.001) after adjusting for confounders. The linear mixed model showed a change in left-right SctO2 over the first 30 min after OLV that was statistically significant (coefficient, -0.042; 95% CI, -0.070--0.014; P = 0.004). For the left-right SctO2 correlation during OLV in each patient, 62.9% (78/124) patients showed a strong correlation, 19.4% (24/124) a medium correlation, and the rest a poor correlation. The maximal difference between the left and right SctO2 was 13.5 (9.0, 20.0). Multivariate analysis showed that it was not associated with delirium (odds ratio [OR], 1.023; 95% CI, 0.963-1.087; P = 0.463). CONCLUSIONS: The correlation between left and right SctO2 was affected by one-lung ventilation in patients undergoing lung cancer surgery. This result indicates the requirement of bilateral SctO2 monitoring to reflect brain oxygenation. TRIAL REGISTRATION: This study was a secondary analysis of a cohort study approved by the Clinical Research Review Board of Peking University First Hospital (#2017-1378) and was registered in the Chinese Clinical Trial Registry on 10/09/2017 ( http://www.chictr.org.cn , ChiCTR-ROC-17012627).

Convolutional neural network based anatomical site identification for laryngoscopy quality control: A multicenter study.

OBJECTIVES: Video laryngoscopy is an important diagnostic tool for head and neck cancers. The artificial intelligence (AI) system has been shown to monitor blind spots during esophagogastroduodenoscopy. This study aimed to test the performance of AI-driven intelligent laryngoscopy monitoring assistant (ILMA) for landmark anatomical sites identification on laryngoscopic images and videos based on a convolutional neural network (CNN). MATERIALS AND METHODS: The laryngoscopic images taken from January to December 2018 were retrospectively collected, and ILMA was developed using the CNN model of Inception-ResNet-v2 + Squeeze-and-Excitation Networks (SENet). A total of 16,000 laryngoscopic images were used for training. These were assigned to 20 landmark anatomical sites covering six major head and neck regions. In addition, the performance of ILMA in identifying anatomical sites was validated using 4000 laryngoscopic images and 25 videos provided by five other tertiary hospitals. RESULTS: ILMA identified the 20 anatomical sites on the laryngoscopic images with a total accuracy of 97.60 %, and the average sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 100 %, 99.87 %, 97.65 %, and 99.87 %, respectively. In addition, multicenter clinical verification displayed that the accuracy of ILMA in identifying the 20 targeted anatomical sites in 25 laryngoscopic videos from five hospitals was ≥95 %. CONCLUSION: The proposed CNN-based ILMA model can rapidly and accurately identify the anatomical sites on laryngoscopic images. The model can reflect the coverage of anatomical regions of the head and neck by laryngoscopy, showing application potential in improving the quality of laryngoscopy.

Four New Polyhydroxy Cyclohexanes from the Stems of Fissistigma tientangense.

Four undescribed polyhydroxy cyclohexanes, fissoxhydrylenes A-D (1-4), together with two known biogenetically related polyhydroxy cyclohexanes (5 and 6) were isolated from the stems of Fissistigma tientangense Tsiang et P. T. Li. Their structures were elucidated by detailed analysis of NMR, HR-ESI-MS, IR, UV and Optical rotations data. The absolute configuration of 1 was confirmed by X-ray crystallographic. The absolute configurations of 2-4 were confirmed by chemical reaction and optical rotations. Compound 4 represent the first example of a no substituent polyhydroxy cyclohexanes from natural products. All isolated compounds were evaluated for their anti-inflammatory activities against the lipopolysaccharide-induced nitric oxide (NO) production in mouse macrophage RAW 264.7 cells in vitro. Compounds 3 and 4 showed inhibitory activities with the IC50 values of 16.63±0.06 µM and 14.38±0.08 µM, respectively.