Efficacy and safety of sympathetic mapping and ablation of renal nerves for the treatment of hypertension (SMART): 6-month follow-up of a randomised, controlled trial.

Background: Previous trials of renal denervation (RDN) have been designed to investigate reduction of blood pressure (BP) as the primary efficacy endpoint using non-selective RDN without intraoperatively verified RDN success. It is an unmet clinical need to map renal nerves, selectively denervate renal sympathetic nerves, provide readouts for the interventionalists and avoid futile RDN. We aimed to examine the safety and efficacy of renal nerve mapping/selective renal denervation (msRDN) in patients with uncontrolled hypertension (HTN) and determine whether antihypertensive drug burden is reduced while office systolic BP (OSBP) is controlled to target level (＜140 mmHg). Methods: We conducted a randomized, prospective, multicenter, single-blinded, sham-controlled trial. The study combined two efficacy endpoints at 6 months as primary outcomes: The control rate of patients with OSBP ＜140 mmHg (non-inferior outcome) and change in the composite index of antihypertensive drugs (Drug Index) in the treatment versus Sham group (superior outcome). This design avoids confounding from excess drug-taking in the Sham group. Antihypertensive drug burden was assessed by a composite index constructed as: Class N (number of classes of antihypertensive drugs) × (sum of doses). 15 hospitals in China participated in the study and 220 patients were enrolled in a 1:1 ratio (msRDN vs Sham). The key inclusion criteria included: age (18-65 years old), history of essential HTN (at least 6 months), heart rate (≥70 bpm), OSBP (≥150 mmHg and ≤180 mmHg), ambulatory BP monitoring (ABPM, 24-h SBP ≥130 mmHg or daytime SBP ≥135 mmHg or nighttime SBP ≥120 mmHg), renal artery stenosis (＜50%) and renal function (eGFR ＞45 mL/min/1.73 m2). The catheter with both stimulation and ablation functions was inserted in the distal renal main artery. The RDN site (hot spot) was selected if SBP increased (≥5 mmHg) by intra-renal artery (RA) electrical stimulation; an adequate RDN was confirmed by repeated electronic stimulation if no increase in BP otherwise, a 2nd ablation was performed at the same site. At sites where there was decreased SBP (≥5 mmHg, cold spot) or no BP response (neutral spot) to stimulation, no ablation was performed. The mapping, ablation and confirmation procedure was repeated until the entire renal main artery had been tested then either treated or avoided. After msRDN, patients had to follow a predefined, vigorous drug titration regimen in order to achieve target OSBP (＜140 mmHg). Drug adherence was monitored by liquid chromatography-tandem mass spectrometry analysis using urine. This study is registered with ClinicalTrials.gov (NCT02761811) and 5-year follow-up is ongoing. Findings: Between July 8, 2016 and February 23, 2022, 611 patients were consented, 220 patients were enrolled in the study who received standardized antihypertensive drug treatments (at least two drugs) for at least 28 days, presented OSBP ≥150 mmHg and ≤180 mmHg and met all inclusion and exclusion criteria. In left RA and right RA, mapped sites were 8.2 (3.0) and 8.0 (2.7), hot/ablated sites were 3.7 (1.4) and 4.0 (1.6), cold spots were 2.4 (2.6) and 2.0 (2.2), neutral spots were 2.0 (2.1) and 2.0 (2.1), respectively. Hot, cold and neutral spots was 48.0%, 27.5% and 24.4% of total mapped sites, respectively. At 6 M, the Control Rate of OSBP was comparable between msRDN and Sham group (95.4% vs 92.8%, p = 0.429), achieved non-inferiority margin -10% (2.69%; 95% CI -4.11%, 9.83%, p ＜ 0.001 for non-inferiority); the change in Drug Index was significantly lower in msRDN group compared to Sham group (4.37 (6.65) vs 7.61 (10.31), p = 0.010) and superior to Sham group (-3.25; 95% CI -5.56, -0.94, p = 0.003), indicating msRDN patients need significantly fewer drugs to control OSBP ＜140 mmHg. 24-hour ambulatory SBP decreased from 146.8 (13.9) mmHg by 10.8 (14.1) mmHg, and from 149.8 (12.8) mmHg by 10.0 (14.0) mmHg in msRDN and Sham groups, respectively (p < 0.001 from Baseline; p > 0.05 between groups). Safety profiles were comparable between msRDN and Sham groups, demonstrating the safety and efficacy of renal mapping/selective RDN to treat uncontrolled HTN. Interpretation: The msRDN therapy achieved the goals of reducing the drug burden of HTN patients and controlling OSBP <140 mmHg, with only approximately four targeted ablations per renal main artery, much lower than in previous trials. Funding: SyMap Medical (Suzhou), LTD, Suzhou, China.

Combined Effect of Underlayer and Deposition Solution to Optimize the Alignment of Hematite Photoanodes.

This study investigates the optimization of hematite (α-Fe2O3) photoanodes for enhanced photoelectrochemical (PEC) performance and reproducibility, which are crucial for photocatalytic applications. Despite hematite's potential, hindered by inherent limitations, significant improvements were realized by introducing a titanium dioxide (TiO2) underlayer and ethanol-modified deposition. The influence of the deposition methods was understood by potential-dependent photoelectrochemical impedance spectroscopy analysis. The introduction of the TiO2 underlayer effectively increased the density of states, preferable for the electron transport in the bulk hematite, and the ethanol deposition on a TiO2 underlayer led to a stable surface state formation (S1 state) for the photoexcited hole transfer. This analysis illuminated the intricate interplay between electron transport in the bulk and photogenerated hole transfer at the solution interface, thereby facilitating smoother charge transfer. These findings underscore the viability of surface engineering and meticulous process optimization in addressing critical challenges in photocatalyst development.

Cocatalyst activity mapping for photocatalytic materials revealed by the pattern-illumination time-resolved phase microscopy.

Photocatalytic water-splitting represents a promising avenue for clean hydrogen production, necessitating an in-depth understanding of the photocatalytic reaction mechanism. The majority of the photocatalytic materials need cocatalysts to enhance the photo-oxidation or reduction reactions. However, the working mechanism, such as collecting charge carriers or reducing the reaction barrier, is not clear because they disperse inhomogeneously on a surface, and it is difficult to follow the local charge carrier behavior. This study employs the pattern-illumination time-resolved phase microscopy (PI-PM) method to unravel the spatial charge carrier behavior in photocatalytic systems, utilizing time-resolved microscopic image (refractive index change) sequences and their clustering analyses. This approach is robust for studying the change in local charge carrier behavior. We studied two major cocatalyst effects on photocatalysts: TiO2 with/without Pt and hematite with/without CoPi. The PI-PM method, supported by charge type clustering and the effects of scavengers, allowed for the analysis of local activity influenced by cocatalysts. This approach revealed that the introduction of cocatalysts alters the local distribution of charge carrier behavior and significantly impacts their decay rates. In TiO2 systems, the presence of Pt cocatalysts led to a local electron site on the micron scale, extending the lifetime to a few tens of microseconds from a few microseconds. Similarly, in hematite films with CoPi, we observed a notable accumulation of holes at cocatalyst sites, emphasizing the role of cocatalysts in enhancing photocatalytic efficiency. The study's findings highlight the complexity of charge carrier dynamics in photocatalytic processes and the significant influence of cocatalysts.

Homeopathic Ankle Dislocation for Treatment of Unstable Trimalleolar Fractures Involving Posterior Die-Punch Fragment: A Retrospective Cohort Study.

OBJECTIVES: Unstable trimalleolar fractures are relatively complex and more difficult to manage if die-punch fracture is present. We aimed to evaluate the curative effect of homeopathic ankle dislocation on the unstable trimalleolar fractures involving posterior die-punch fragments. METHODS: A total of 124 patients diagnosed with unstable trimalleolar fractures combined with post-die punch fragment between June 2008 and June 2020 were retrospectively included. Patients who received homeopathic ankle dislocation were named as the experimental group, and patients who accepted conventional treatment were control group. The fracture healing time, wound healing, American Orthopedic Foot and Ankle Society ankle-hindfoot scale (AOFAS), visual analogue scale (VAS), the Kellgren-Lawrence arthritis grading scale (KLAGS) and short-form 36 score (SF-36) scores were collected. Student t-test was used for fracture healing time. Wound healing and SF-36 were compared using the Mann-Whitney test. Repeated measurement analysis of variance (ANOVA) was used for AOFAS and VAS. χ2-test was used for KLAGS. RESULTS: AOFAS showed statistically significant differences between the two groups (p = 0.001). In non-weight-bearing and weight-bearing conditions, VAS scores were significant different between the two groups, and there was an interaction between group and time point (p < 0.001). The experimental group was superior to the control group in terms of physical function (p = 0.022), role-physical (p = 0.018), general health (p = 0.001) and social function (p = 0.042).The operation time of experimental group was shorter than that of control group (p < 0.001). CONCLUSION: Homeopathic ankle dislocation is used for the unstable trimalleolar fractures involving posterior die-punch fragment, which can provide better functional outcomes while shortening the operation time and recovery period.

Cost-effectiveness analysis of toripalimab plus chemotherapy for patients with advanced esophageal squamous cell carcinoma in China.

BACKGROUND: The aim of the current analysis was to evaluate the cost-effectiveness of toripalimab plus chemotherapy compared with chemotherapy alone as the first-line option for patients with advanced esophageal squamous cell carcinoma (ESCC) from the perspective of Chinese health-care system. METHODS: A partitioned survival model was conducted to track 3-week patients' transition and evaluate the health and economic outcomes in 10-year horizon of the two competing first-line treatment among toripalimab plus chemotherapy and chemotherapy alone. The survival data were gathered from the JUPITER-06 trial, and cost and utility values were obtained from the local charges and published studies. Total costs, life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were the model outcomes. Sensitivity and subgroup analyses were conducted. RESULTS: Treatment with toripalimab plus chemotherapy yields marginal cost of $8,639.74 and additional 0.65 QALYs, resulting in an ICER of $13,280.97 per additional QALY gained, which was lower than the willingness-to-pay (WTP) threshold of $38,224 in China. Sensitivity and subgroup analyses confirmed the robustness of the model outcomes. CONCLUSIONS: Toripalimab plus chemotherapy was likely to be the cost-effective first-line option for patients with advanced ESCC compared with chemotherapy alone with the WTP threshold of $38,224 per additional QALY gained from the perspective of the Chinese health-care system.

Identification of the Contributing Factors to the Photoelectric Conversion Efficiency for Hematite Photoanodes by Using Machine Learning.

Hematite has gained significant attention in the field of photocatalysis as one of the most promising materials for the photoanode of photoelectrochemical (PEC) water splitting due to visible light absorption and the abundance of availability. However, its performance improvement process suffers from a serious bottleneck due to "sample variation" and "inactivity". However, the physical origin of them has not yet been elucidated. To address these issues, we have developed a machine learning (ML) strategy using a combination of various analytical data of hematite photoanodes to discern "active/inactive" and identify the dominant factors. For the demonstration purpose of the ML strategy, we picked up one of the dominant factors, the interfacial resistivity between hematite and FTO, which has not generally been explored as a first candidate in the improvement of photocatalytic materials. The operational parameters for the sample preparation were optimized to modify the selected physical property. Along with the improvement of the selected resistivity, we found that the other dominant descriptors related to the properties of bulk hematite and the surface facet were also modified and help improve the PEC performance.

An Oxysulfide Photocatalyst Evolving Hydrogen with an Apparent Quantum Efficiency of 30 % under Visible Light.

Photocatalytic water splitting is a simple means of converting solar energy into storable hydrogen energy. Narrow-band gap oxysulfide photocatalysts have attracted much attention in this regard owing to the significant visible-light absorption and relatively high stability of these compounds. However, existing materials suffer from low efficiencies due to difficulties in synthesizing these oxysulfides with suitable degrees of crystallinity and particle sizes, and in constructing effective reaction sites. The present work demonstrates the production of a Gd2 Ti2 O5 S2 (λ<650 nm) photocatalyst capable of efficiently driving photocatalytic reactions. Single-crystalline, plate-like Gd2 Ti2 O5 S2 particles with atomically ordered surfaces were synthesized by flux and chemical etching methods. Ultrafine Pt-IrO2 cocatalyst particles that promoted hydrogen (H2 ) and oxygen (O2 ) evolution reactions were subsequently loaded on the Gd2 Ti2 O5 S2 while ensuring an intimate contact by employing a microwave-heating technique. The optimized Gd2 Ti2 O5 S2 was found to evolve H2 from an aqueous methanol solution with a remarkable apparent quantum efficiency of 30 % at 420 nm. This material was also stable during O2 evolution in the presence of a sacrificial reagent. The results presented herein demonstrates a highly efficient narrow-band gap oxysulfide photocatalyst with potential applications in practical solar hydrogen production.

Co-doping of a La5Ti2Cu0.9Ag0.1O7S5 photocatalyst (λ < 700 nm) with Ga and Al to enhance photocatalytic H2 evolution.

La5Ti2Cu0.9Ag0.1O7S5 (LTCA) (λ < 700 nm) can function as a photocatalyst for H2 evolution. Co-doping LTCA with Ga3+ and Al3+ at Ti4+ sites effectively enhanced the H2 evolution activity of LTCA, yielding an apparent quantum efficiency of 18% at 420 nm. The activity of this material was greater than that previously reported for Ga-doped LTCA by a factor of 1.6. Such activity enhancement is attributed to increasing the population of long-lived photogenerated electrons and facilitating the electron transfer to the cocatalyst. This work significantly improved the LTCA-based photocatalyst for H2 evolution, making it a promising material for future application in non-sacrificial Z-scheme water splitting.

A general interfacial-energetics-tuning strategy for enhanced artificial photosynthesis.

The demands for cost-effective solar fuels have triggered extensive research in artificial photosynthesis, yet the efforts in designing high-performance particulate photocatalysts are largely impeded by inefficient charge separation. Because charge separation in a particulate photocatalyst is driven by asymmetric interfacial energetics between its reduction and oxidation sites, enhancing this process demands nanoscale tuning of interfacial energetics on the prerequisite of not impairing the kinetics and selectivity for surface reactions. In this study, we realize this target with a general strategy involving the application of a core/shell type cocatalyst that is demonstrated on various photocatalytic systems. The promising H2O2 generation efficiency validate our perspective on tuning interfacial energetics for enhanced charge separation and photosynthesis performance. Particularly, this strategy is highlighted on a BiVO4 system for overall H2O2 photosynthesis with a solar-to-H2O2 conversion of 0.73%.

Development and validation of a screening model for lung cancer using machine learning: A large-scale, multi-center study of biomarkers in breath.

Objectives: Lung cancer (LC) is the largest single cause of death from cancer worldwide, and the lack of effective screening methods for early detection currently results in unsatisfactory curative treatments. We herein aimed to use breath analysis, a noninvasive and very simple method, to identify and validate biomarkers in breath for the screening of lung cancer. Materials and methods: We enrolled a total of 2308 participants from two centers for online breath analyses using proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS). The derivation cohort included 1007 patients with primary LC and 1036 healthy controls, and the external validation cohort included 158 LC patients and 107 healthy controls. We used eXtreme Gradient Boosting (XGBoost) to create a panel of predictive features and derived a prediction model to identify LC. The optimal number of features was determined by the greatest area under the receiver-operating characteristic (ROC) curve (AUC). Results: Six features were defined as a breath-biomarkers panel for the detection of LC. In the training dataset, the model had an AUC of 0.963 (95% CI, 0.941-0.982), and a sensitivity of 87.1% and specificity of 93.5% at a positivity threshold of 0.5. Our model was tested on the independent validation dataset and achieved an AUC of 0.771 (0.718-0.823), and sensitivity of 67.7% and specificity of 73.0%. Conclusion: Our results suggested that breath analysis may serve as a valid method in screening lung cancer in a borderline population prior to hospital visits. Although our breath-biomarker panel is noninvasive, quick, and simple to use, it will require further calibration and validation in a prospective study within a primary care setting.

Repair effect of photobiomodulation combined with human umbilical cord mesenchymal stem cells on rats with acute lung injury.

Acute lung injury (ALI) impaired the function of blood oxygen exchange function, resulting in tissue hypoxia and patient death. Recently, human umbilical cord mesenchymal stem cells (hUCMSCs) are thought to mitigate the effects of ALI, which boosts researchers' interest in employing stem cell-based therapies to manage ALI. However, as a novel therapy, hUCMSCs still face various limitations such as migrating weakly and insufficient proliferation in vivo. Photobiomodulation (PBM) effciently promotes cell proliferation, migration and homing, which presents a promising strategy for overcoming above limitations. In this study, PBM was emerged to intervene hUCMSCs through detecting cell proliferation, oxidative stress-related factors and inflammatory factors. These results assuredly confirmed that PBM enhanced the antioxidant capacity of cells and improved cell survival in vitro experiments. In vivo, PBM-intervened hUCMSCs intuitively reduce thickness of alveolar septum, excessive secretion of inflammatory factors, relieves bleeding, edema and fibrosis. As a physical intervention, PBM further strengthens the therapeutic effect of hUCMSCs and depicted a hopeful therapy in ALI treatment.

Local charge carrier dynamics of a particulate Ga-doped La5Ti2Cu0.9Ag0.1O7S5 photocatalyst and the impact of Rh cocatalysts.

Visible-light responsive photocatalytic materials are expected to be deployed for practical use in photocatalytic water splitting. One of the promising materials as a p-type semiconductor, oxysulfides, was investigated in terms of the local charge carrier behavior for each particle by using a home-built time-resolved microscopic technique in combination with clustering analysis. We could differentiate electron and hole trapping to the surface states and the following recombination on a micron-scale from the nanosecond to microsecond order. The map of the charge carrier type revealed that charge trapping sites for electrons and holes were spatially separated within each particle/aggregate. Furthermore, the effect of the rhodium cocatalyst was recognized as a new electron pathway, trapping to the rhodium site and the following recombination, which was delayed compared with the original electron recombination process. The Rh effect was discussed based on the phenomenological simulation, revealing a possible reason for the decay was due to the anisotropic diffusion of charge carriers in oxysulfides or the interfacial energy barrier at the interface.

Development and Validation of a Combined Hypoxia and Immune Prognostic Classifier for Lung Adenocarcinoma.

Lung cancer is the leading cause of cancer-related deaths worldwide. Hypoxia is a crucial microenvironmental factor in lung adenocarcinoma (LUAD). However, the prognostic value based on hypoxia and immune in LUAD remains to be further clarified. The hypoxia-related genes (HRGs) and immune-related genes (IRGs) were downloaded from the public database. The RNA-seq expression and matched complete clinical data for LUAD were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to model construction. Hypoxia expression profiles, immune cell infiltration, functional enrichment analysis, Tumor Immune Dysfunction and Exclusion (TIDE) score and the somatic mutation status were analyzed and compared based on the model. Moreover, immunofluorescence (IF) staining in human LUAD cases to explore the expression of hypoxia marker and immune checkpoint. A prognostic model of 9 genes was established, which can divide patients into two subgroups. There were obvious differences in hypoxia and immune characteristics in the two groups, the group with high-risk score value showed significantly high expression of hypoxia genes and programmed death ligand-1 (PD-L1), and maybe more sensitive to immunotherapy. Patients in the high-risk group had shorter overall survival (OS). This model has a good predictive value for the prognosis of LUAD. We constructed a new HRGs and IRGs model for prognostic prediction of LUAD. This model may benefit future immunotherapy for LUAD.

Combining EGFR-TKI With SAHA Overcomes EGFR-TKI-Acquired Resistance by Reducing the Protective Autophagy in Non-Small Cell Lung Cancer.

Nowadays, lung cancer has the highest mortality worldwide. The emergence of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has greatly improved the survival of patients with non-small cell lung cancer (NSCLC) having EGFR-TKI-sensitive mutations. Unfortunately, acquired resistance happens for most patients. In the present research, we found that EGFR-TKIs (such as gefitinib and osimertinib) can induce autophagy in NSCLC cell lines. Compared with parental sensitive cells, drug-resistant cells have higher autophagy activity. The use of an autophagy inhibitor could enhance the toxicity of gefitinib and osimertinib, which indicates that the enhancement of protective autophagy might be one of the mechanisms of EGFR-TKI resistance in NSCLC. In addition, increased autophagy activity is associated with decreased enhancer of zeste homolog 2 (EZH2) expression. Knockdown of EZH2 or EZH2 inhibitor treatment could lead to increased autophagy in NSCLC cells, indicating that EZH2 is a negative regulator of autophagy. We revealed that the increase in autophagy caused by the reduction of EZH2 was reversed in vitro and in vivo when combining gefitinib or osimertinib with suberoylanilide hydroxamic acid (SAHA), a broad-spectrum histone deacetylase inhibitor (HDACi). In conclusion, our results indicated that the combination of EGFR-TKIs and SAHA may be a new strategy to overcome EGFR-TKIs acquired resistance.

ROCK inhibitor fasudil reduces the expression of inflammatory factors in LPS-induced rat pulmonary microvascular endothelial cells via ROS/NF-κB pathway.

BACKGROUND: Inflammation plays a major role in the pulmonary artery hypertension (PAH) and the acute lung injury (ALI) diseases. The common feature of these complications is the dysfunction of pulmonary microvascular endothelial cells (PMVECs). Fasudil, the only Rho kinase (ROCK) inhibitor used in clinic, has been proved to be the most promising new drug for the treatment of PAH, with some anti-inflammatory activity. Therefore, in the present study, the effect of fasudil on lipopolysaccharide (LPS)-induced inflammatory injury in rat PMVECs was investigated. METHODS: LPS was used to make inflammatory injury model of rat PMVECs. Thereafter, the mRNA and protein expression of pro-inflammatory factors was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) assay respectively. Intracellular reactive oxygen species (ROS) levels were measured by the confocal laser scanning system. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA) were determined by using commercial kits according to the manufacturer's instructions. Western blot assay was used to detect the protein expression of nuclear factor kappa B (NF-κB) p65. RESULTS: Fasudil effectively prevented inflammatory injury induced by LPS, which is manifested by the decrease of pro-inflammatory cytokines interleukin-6 (IL-6) and monocyte chenotactic protein-1 (MCP-1). Meanwhile, fasudil dramatically reduced the levels of ROS and MDA, and also elevated the activities of SOD and GSH-Px. Furthermore, the nuclear translocation of NF-κB p65 induced by LPS was also suppressed by fasudil. Additionally, the ROS scavengers N-Acetylcysteine (N-Ace) was also found to inhibit the nuclear translocation of NF-κB and the mRNA expression of IL-6 and MCP-1 induced by LPS, which suggested that ROS was essential for the nuclear translocation of NF-κB. CONCLUSIONS: The present study revealed that fasudil reduced the expression of inflammatory factors, alleviated the inflammatory and oxidative damage induced by LPS in rat PMVECs via ROS-NF-κB signaling pathway.

Pyroptosis-Related LncRNA Signatures Correlate With Lung Adenocarcinoma Prognosis.

Background: Pyroptosis is a new type of programmed cell death, accompanied by an intense inflammatory response. Previous studies have shown that pyroptosis can modify long-chain non-coding RNA (lncRNA), thereby affecting the occurrence and progression of tumors. However, the underlying role of pyroptosis-related lncRNA in lung adenocarcinoma (LUAD) remains to be elucidated. Therefore, the purpose of our study was to evaluate the prognostic value of pyrolysis-related lncRNA in patients with LUAD. Methods: A total of 454 LUAD samples were downloaded from The Cancer Genome Atlas (TCGA) database. Pearson's correlation coefficient was used to identify the pyroptosis-related lncRNAs. Unsupervised consensus clustering was used to identify the various LUAD molecular subtypes. A least absolute shrinkage and selection operator (LASSO) analysis was conducted to construct a prognostic signature. Results: An 11-lncRNA prognostic signature out of 19 identified pyroptosis-related prognostic lncRNAs was constructed. The patients with LUAD were divided into low-risk and high-risk groups. Patients in the high-risk group had higher score values and mortality. The immune score, stromal score, and estimate score were lower in the high-risk group. The risk score was an independent predictor for OS in multivariate Cox regression analyses (HR > 1, p < 0.01). BTLA, PD-1, PD-L1, CTLA, and CD47 were lower expressed in the high-risk group. Conclusions: Our study identified an 11-pyroptosis-related lncRNA signature. These findings could further clarify the role of pyroptosis in LUAD and guide the prognosis and individualized treatment of patients.

[Lung Cancer Stem-like Cells and Drug Resistance].

Lung cancer remains the leading cause of cancer-related death world-wide. Therapy resistance and relapse are considered major reasons contributing to the poor survival rates of lung cancer. Accumulated evidences have demonstrated that a small subpopulation of stem-like cells existed within lung cancer tissues and cell lines, possessing the abilities of self-renewal, multipotent differentiation and unlimited proliferation. These lung cancer stem-like cells (LCSCs) can generate tumors with high effeciency in vivo, survive cytotoxic therapies, and eventually lead to therapy resistance and recurrence. In this review, we would like to present recent knowledges on LCSCs, including the origins where they come from, the molecular features to identify them, and key mechanisms for them to survive and develop resistance, in order to provide a better view for targeting them in future clinic.
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Overall photosynthesis of H2O2 by an inorganic semiconductor.

Artificial photosynthesis of H2O2 using earth-abundant water and oxygen is a promising approach to achieve scalable and cost-effective solar fuel production. Recent studies on this topic have made significant progress, yet are mainly focused on using  organic polymers. This set of photocatalysts is susceptible to potent oxidants (e.g. hydroxyl radical) that are inevitably formed during H2O2 generation. Here, we report an inorganic Mo-doped faceted BiVO4 (Mo:BiVO4) system that is resistant to radical oxidation and exhibits a high overall H2O2 photosynthesis efficiency among inorganic photocatalysts, with an apparent quantum yield of 1.2% and a solar-to-chemical conversion efficiency of 0.29% at full spectrum, as well as an apparent quantum yield of 5.8% at 420 nm. The surface-reaction kinetics and selectivity of Mo:BiVO4 were tuned by precisely loading CoOx and Pd on {110} and {010} facets, respectively. Time-resolved spectroscopic investigations of photocarriers suggest that depositing select cocatalysts on distinct facet tailored the interfacial energetics between {110} and {010} facets and enhanced charge separation in Mo:BiVO4, therefore overcoming a key challenge in developing efficient inorganic photocatalysts. The promising H2O2 generation efficiency achieved by delicate design of catalyst spatial and electronic structures sheds light on applying robust inorganic particulate photocatalysts to artificial photosynthesis of H2O2.

Collaborative obstacle avoidance algorithm of multiple bionic snake robots in fluid based on IB-LBM.

This paper presents a collaborative obstacle avoidance algorithm of multiple bionic snake robots in fluid based on IB-LBM. The method can make the multiple bionic snake robots avoid different obstacles in the fluid under the control of the improved Serpenoid curve function. The proposed method has high parallelism, can simulate the complex non-linear phenomenon of the multiple snake robots, deal with the complex boundary conditions of the robot, and reduce the conversion of the computational grid. Firstly, a non-linear fluid model is established by LBM, which solves the non-linear problem that the classical Navier-Stokes equations cannot explain the random motion. Secondly, the force source boundary model of multiple bionic snake robots is established by IBM, which saves the calculation time, improves the calculation efficiency and system stability. After that, each bionic snake robot is given a special force to make the robots collaborate with each other and non-colliding with each other in the process of the obstacle avoidance. Finally, through simulation experiments, the trajectory of multiple bionic snake robots avoiding different number of the obstacles in the fluid is analyzed and the collaborative obstacle avoidance process of multiple bionic snake robots in fluid is observed. The validity of the collaborative obstacle avoidance algorithm of multiple bionic snake robots in fluid based on the IB-LBM is verified.

Single-Cell Transcriptomics Unveils the Dedifferentiation Mechanism of Lung Adenocarcinoma Stem Cells.

Lung adenocarcinoma (LUAD) is a major subtype of lung cancer, and its prognosis is still poor due to therapy resistance, metastasis, and recurrence. In recent years, increasing evidence has shown that the existence of lung cancer stem cells is responsible for the propagation, metastasis, therapy resistance, and recurrence of the tumor. During their transition to cancer stem cells, tumor cells need to inhibit cell differentiation and acquire invasive characteristics. However, our understanding of the property and role of such lung cancer stem cells is still limited. In this study, lung adenocarcinoma cancer stem cells (LCSCs) were enriched from the PC-9 cell line in a serum-free condition. PC-9 cells grew into spheres and showed higher survival rates when exposed to gefitinib: the drug used for the treatment of LUAD. Additionally, we found that the canonical stemness marker protein CD44 was significantly increased in the enriched LCSCs. Then, LCSCs were inoculated into the groin of nude mice for 1.5 months, and tumors were detected in the animals, indicating the strong stemness of the cells. After that, we performed single-cell RNA sequencing (scRNA-seq) on 7320 LCSCs and explored the changes in their transcriptomic signatures. We identified cell populations with a heterogeneous expression of cancer stem marker genes in LCSCs and subsets with different degrees of differentiation. Further analyses revealed that the activation of the FOXM1 (oncoprotein) transcription factor is a key factor in cell dedifferentiation, which enables tumor cells to acquire an epithelial-mesenchymal transition phenotype and increases the LCSC surface marker CD44. Moreover, we found that the combination of CD44, ABCG2, and ALCAM was a specific marker for LCSCs. In summary, this study identified the potential factors and molecular mechanisms underlying the stemness properties of LUAD cancer cells; it could also provide insight into developing novel and effective therapeutic approaches.