Single-cell and spatial proteo-transcriptomic profiling reveals immune infiltration heterogeneity associated with neuroendocrine features in small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive pulmonary neuroendocrine malignancy featured by cold tumor immune microenvironment (TIME), limited benefit from immunotherapy, and poor survival. The spatial heterogeneity of TIME significantly associated with anti-tumor immunity has not been systemically studied in SCLC. We performed ultra-high-plex Digital Spatial Profiling on 132 tissue microarray cores from 44 treatment-naive limited-stage SCLC tumors. Incorporating single-cell RNA-sequencing data from a local cohort and published SCLC data, we established a spatial proteo-transcriptomic landscape covering over 18,000 genes and 60 key immuno-oncology proteins that participate in signaling pathways affecting tumorigenesis, immune regulation, and cancer metabolism across 3 pathologically defined spatial compartments (pan-CK-positive tumor nest; CD45/CD3-positive tumor stroma; para-tumor). Our study depicted the spatial transcriptomic and proteomic TIME architecture of SCLC, indicating clear intra-tumor heterogeneity dictated via canonical neuroendocrine subtyping markers; revealed the enrichment of innate immune cells and functionally impaired B cells in tumor nest and suggested potentially important immunoregulatory roles of monocytes/macrophages. We identified RE1 silencing factor (REST) as a potential biomarker for SCLC associated with low neuroendocrine features, more active anti-tumor immunity, and prolonged survival.

Four novel species of Pleurotheciaceae collected from freshwater habitats in Jiangxi Province, China.

During an investigation of fungal diversity from freshwater environments in different regions in Jiangxi Province, China, four interesting species were collected. Morphology coupled with combined gene analysis of an ITS, LSU, SSU, and rpb2 DNA sequence data showed that they belong to the family Pleurotheciaceae. Four new species, Pleurotheciella ganzhouensis, Pla. irregularis, Pla. verrucosa, and Pleurothecium jiangxiense are herein described. Pleurotheciella ganzhouensis is characterized by its capsule-shaped conidia and short conidiophores, while Pla. irregularis has amorphous conidiophores and 3-septate conidia. Pleurotheciella verrucosa has cylindrical or verrucolose conidiogenous cells, 1-septate, narrowly fusiform, meniscus or subclavate conidia. Pleurothecium jiangxiense characterized in having conidiogenous cells with dense cylindrical denticles and short conidiophores. Pleurothecium obovoideum was transferred to Neomonodictys based on phylogenetic evidence. All species are compared with other similar species and comprehensive descriptions, micrographs, and phylogenetic data are provided.

Application of earthworm can enhance biological power generation and accelerate sulfamethoxazole removal in agricultural soils.

Microbial degradation plays a crucial role in removing sulfonamides from soil, enhancing sulfamethoxazole (SMX) remediation. To further augment SMX removal efficiency and mitigate the transmission risk associated with antibiotic resistance genes (ARGs), this study proposes a novel approach that integrates micro-animals, microorganisms, and microbial fuel cell (MFC) technology. The results showed that earthworm-MFC synergy substantially reduces SMX content and ARGs abundance in soil. The introduction of earthworms enhances humus content, facilitating electron transfer within MFC and consequently improving current generation. Furthermore, electrical stimulation applied to earthworms led to increased protein secretion and enhanced antioxidant system activity, thereby accelerating SMX degradation. Earthworms also foster MFC-associated bacterial growth and SMX-degrading bacteria proliferation, augmenting MFC treatment efficacy. This synergistic effect significantly augmented the overall efficacy of MFC treatment for antibiotics. Overall, integrating earthworm activity with MFC technology effectively optimizes electricity generation and enhances pollutant removal.

Fiber-integrated quantum microscopy system for cells.

Quantum entanglement serves as an essential resource across various fields, including quantum communication, quantum computing, and quantum precision measurement. Quantum microscope, as one of the significant applications in quantum precision measurement, could bring revolutionary advancements in both signal-to-noise ratio (SNR) and spatial resolution of imaging. Here, we present a quantum microscopy system that relies on a fully fiber-integrated high-performance energy-time entangled light source operating within the near-infrared II (NIR-II) window. Complemented by tailored real-time data acquisition and processing software, we successfully demonstrate the quantum imaging of a standard target, achieving a SNR of 131.51 ± 6.74 and a spatial resolution of 4.75 ± 0.27 µm. Furthermore, we showcase quantum imaging of cancer cells, unveiling the potential of quantum entanglement in biomedical applications. Our fiber-integrated quantum microscope, characterized by high imaging SNR, instantaneous image capture, and analysis capabilities, marks an important step toward the practical application in life sciences.

Long-term clinical efficacy of drug-coated balloon angioplasty for TASCII C/D femoropopliteal lesions in older patients with chronic limb-threatening ischemia: A retrospective study.

This study aimed to evaluate the long-term clinical outcomes of drug-coated drug (DCB) angioplasty for long femoropopliteal lesions in older patients with chronic limb-threatening ischemia (CLTI). In this multi-center retrospective study, we enrolled 119 patients with CLTI due to Trans-Atlantic Inter-Society Consensus (TASCII) C/D femoropopliteal lesions who underwent DCB angioplasty. A total of 119 patients with 122 limbs (TASCII C = 67, 54.9%; TASCII D = 55, 45.1%) were enrolled. At 36-month follow-up, primary patency, assisted primary patency, secondary patency, and freedom from target lesion revascularization were 47.3%, 49.8%, 59.5%, and 62.7%, respectively, and there was a significant improvement over baseline in Rutherford class (P < .001) and ankle-brachial index measurements (P < .001). Complex target lesions (P = .017) and 1 stenosis-free outflow vessel (P = .001) were risk predictors of freedom from clinically driven target lesion revascularization. Complex target lesions (P = .044), diabetes (P = .007), and 1 stenosis-free outflow vessel (P = .003) were risk predictors of restenosis. At 2 months, the ulcer healing rate was 96.3% (26/27). At 36 months, the limb salvage and survival rates were 85.8% and 83.3%, respectively. DCB angioplasty were safe and effective for older patients with CLTI attributable to femoropopliteal TASCII C/D lesions.

External circuit loading mode regulates anode biofilm electrochemistry and pollutants removal in microbial fuel cells.

This study investigated the effects of different external circuit loading mode on pollutants removal and power generation in microbial fuel cells (MFC). The results indicated that MFC exhibited distinct characteristics of higher maximum power density (Pmax) (named MFC-HP) and lower Pmax (named MFC-LP). And the capacitive properties of bioanodes may affect anodic electrochemistry. Reducing external load to align with the internal resistance increased Pmax of MFC-LP by 54.47 %, without no obvious effect on MFC-HP. However, intermittent external resistance loading (IER) mitigated the biotoxic effects of sulfamethoxazole (SMX) (a persistent organic pollutant) on chemical oxygen demand (COD) and NH4+-N removal and maintained high Pmax (424.33 mW/m2) in MFC-HP. Meanwhile, IER mode enriched electrochemically active bacteria (EAB) and environmental adaptive bacteria Advenella, which may reduce antibiotic resistance genes (ARGs) accumulation. This study suggested that the external circuit control can be effective means to regulate electrochemical characteristics and pollutants removal performance of MFC.

Contributions of Surface Oxidizing Species and Cu+ to the Antibacterial Activities of Cu2O with Different Crystalline Structures.

Although precise regulation of the crystalline structures of metal oxides is an effective method to improve their antibacterial activities, the corresponding mechanisms involved in this process are still unclear. In this study, three kinds of cuprous oxide (Cu2O) samples with different structures of cubes, octahedra, and rhombic dodecahedra (c-Cu2O, o-Cu2O, and r-Cu2O) have been successfully synthesized and their antibacterial activities are compared. The antibacterial activities follow the order of r-Cu2O > o-Cu2O > c-Cu2O, revealing the significant dependence of the antibacterial activities on the crystalline structures of Cu2O. Quenching experiments, as well as the NBT and DPD experiments indicate that ≡CuII─OO• superoxo and ≡CuII─OOH peroxo, instead of •OH, O2•-, and H2O2, are the primary oxidizing species in the oxidative damage to E. coli. Raman analysis further confirms the presence of both ≡CuII─OO• superoxo and ≡CuII─OOH peroxo on the surface of r-Cu2O. On the other hand, the NCP experiment reveals that Cu+, instead of Cu2+, also contributes to the antibacterial process. This study provides new insight into the antibacterial mechanisms of Cu2O.

Rapidly screening of pancreatic lipase inhibitors from Clematis tangutica using affinity ultrafiltration-HPLC-QTOFMS technique combined with targeted separation, in vitro validation, and molecular docking.

INTRODUCTION: Screening of novel pancreatic lipase inhibitors from complex natural products is a meaningful task. OBJECTIVES: Through accurately screening and separating pancreatic lipase inhibitors from Clematis tangutica (C. tangutica), to discover new leading compounds for slimming and accelerate the development and utilization of Tibetan medicine resources. METHODS: An integrated strategy that combines affinity ultrafiltration and high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (AU-HPLC-QTOFMS), targeted separation, in vitro validation, and molecular docking was developed to screen pancreatic lipase inhibitors from C. tangutica. The AU-HPLC-QTOFMS technique was performed to fish for the potential active substances. Macroporous resin, preparative liquid chromatography, and high-speed countercurrent chromatography were implemented for the accurate and targeted separation of active compounds. The inhibitory activities of target compounds to pancreatic lipase were detected by the inhibition experiments in vitro. The binding affinities and binding sites were analyzed using molecular docking. RESULTS: A total of eleven kinds of pancreatic lipase inhibitory substances were screened from C. tangutica. Seven triterpenoid saponins were screened for the first time as lipase inhibitors and successfully prepared with purities higher than 97%. Tanguticoside B, clematangoticoside J, hederoside H1, and rutin showed stronger inhibitory effects with IC50 values of 1.539 ± 0.048, 1.661 ± 0.092, 1.793 ± 0.069, and 1.792 ± 0.094 mmol/l. Moreover, they have the lowest ΔG values of -10.84, -9.97, -10.87, and -9.39 kcal/mol to pancreatic lipase. CONCLUSION: The integrated strategy using AU-HPLC-QTOFMS, targeted separation, in vitro validation, and molecular docking was feasible for rapidly screening and directionally isolating pancreatic lipase inhibitors from C. tangutica.

Role of membrane fouling layer in microbial fuel cell-membrane bioreactor (MFC-MBR) for controlling sulfamethoxazole and corresponding resistance genes.

Integrated MFC-MBR systems effectively remove antibiotics and control the release of antibiotic resistance genes (ARGs). However, the fouling layers on membranes can potentially act as reservoirs for ARGs. This study aims to elucidate the roles of membrane fouling layers and levels in influencing sulfamethoxazole (SMX) removal and ARGs control within an MFC-MBR system. Our findings demonstrate that low-intensity bioelectricity (400-500 mV) mitigates membrane fouling rates. The membrane fouling layer significantly contributes (39%-47%) to SMX removal compared to the cathode/anode zones. Higher extracellular polymeric substance (EPS) content and a lower protein/polysaccharide (PN/PS) ratio favor SMX removal by the membrane fouling layer. Across different levels of membrane fouling, the PN/PS ratio rather than EPS concentration plays a crucial role in SMX removal efficiency. The MFC-MBR with low fouling achieved superior SMX removal (69.1%) compared to medium (54.3%) and high fouling conditions (46.8%). The presence of ARGs in the membrane fouling layer increases with fouling formation, with intrinsic ARGs prevailing. Dense membrane fouling layers effectively retain ARGs, thereby reducing the risk of extracellular ARGs (eARGs) diffusion in effluents. These results provide insights into controlling ARGs in MFC-MBR systems and underscore the significant role of membrane fouling layers in antibiotics and ARGs removal.

A silicon diode-based optoelectronic interface for bidirectional neural modulation.

The development of advanced neural modulation techniques is crucial to neuroscience research and neuroengineering applications. Recently, optical-based, nongenetic modulation approaches have been actively investigated to remotely interrogate the nervous system with high precision. Here, we show that a thin-film, silicon (Si)-based diode device is capable to bidirectionally regulate in vitro and in vivo neural activities upon adjusted illumination. When exposed to high-power and short-pulsed light, the Si diode generates photothermal effects, evoking neuron depolarization and enhancing intracellular calcium dynamics. Conversely, low-power and long-pulsed light on the Si diode hyperpolarizes neurons and reduces calcium activities. Furthermore, the Si diode film mounted on the brain of living mice can activate or suppress cortical activities under varied irradiation conditions. The presented material and device strategies reveal an innovated optoelectronic interface for precise neural modulations.

Concomitant epidermal growth factor receptor mutation/c-ros oncogene 1 rearrangement in non-small cell lung cancer: A case report.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation and c-ros oncogene 1 (ROS1) rearrangement are key genetic alterations and predictive tumor markers for non-small cell lung cancer (NSCLC) and are typically considered to be mutually exclusive. EGFR/ROS1 co-mutation is a rare event, and the standard treatment approach for such cases is still equivocal. CASE SUMMARY: Herein, we report the case of a 64-year-old woman diagnosed with lung adenocarcinoma, with concomitant EGFR L858R mutation and ROS1 rearrangement. The patient received two cycles of chemotherapy after surgery, but the disease progressed. Following 1-month treatment with gefitinib, the disease progressed again. However, after switching to crizotinib, the lesion became stable. Currently, crizotinib has been administered for over 53 months with a remarkable treatment effect. CONCLUSION: The efficacy of EGFR tyrosine kinase inhibitors and crizotinib was vastly different in this NSCLC patient with EGFR/ROS1 co-mutation. This report will aid future treatment of such patients.

Multi-gene phylogenetic analyses revealed two novel species and one new record of Trichobotrys (Pleosporales, Dictyosporiaceae) from China.

The rotting wood in freshwater is a unique eco-environment favoring various fungi. During our investigation of freshwater fungi on decaying wood, three hyphomycetes were collected from Jiangxi and Guangxi Provinces, China. Based on the morphological observations and phylogenetic analysis of a combined DNA data containing ITS, LSU, SSU and tef1-α sequences, two new Trichobotrys species, T.meilingensis and T.yunjushanensis, as well as a new record of T.effusa, were introduced. Additionally, a comprehensive description of the genus with both morphological and molecular data was first provided.

Insights to the cooperation of double-working potential electroactive biofilm for performance of sulfamethoxazole removal: ARG fate and microorganism communities.

Bioelectrochemical systems (BESs) have shown great potential in enhancing sulfamethoxazole (SMX) removal. However, electroactive biofilms (EBs) constructed with single potentials struggle due to limited biocatalytic activity, hindering deep SMX degradation. Here, we constructed a double-working potential BES (BES-D) to investigate its ability to eliminate SMX and reduce the levels of corresponding antibiotic resistance genes (ARGs). The preferable electrochemical activity of EB in BES-D was confirmed by electrochemical characterization, EPS analysis, physical structure, viability of the biofilm, and cytochrome content. BES-D exhibited a notably greater SMX removal efficiency (94.2 %) than did the single-working potential BES (BES-S) and the open-circuit group (OC). Degradation pathway analysis revealed that the cooperative EB could accelerate the in-depth removal of SMX. Moreover, EB interaction in BES-D decreased the relative abundance of ARGs in biofilms compared to that in BES-S, although the absolute number of ARG copies increased in BES-D effluents. Compared to those in BES-S and OC, more complex cross-niche microbial associations in the EB of BES-D were observed by network analysis of the bacterial community and ARG hosts, enhancing the degradation efficiency of SMX. In conclusion, BES-D has significant potential for SMX removal and the enhancement of EB activity. Nonetheless, the risk of ARG dissemination in effluent remains a concern.

GP-Recon: Online Monocular Neural 3D Reconstruction with Geometric Prior.

High-fidelity online 3D scene reconstruction from monocular videos continues to be challenging, especially for coherent and fine-grained geometry reconstruction. The previous learning-based online 3D reconstruction approaches with neural implicit representations have shown a promising ability for coherent scene reconstruction, but often fail to consistently reconstruct fine-grained geometric details during online reconstruction. This paper presents a new on-the-fly monocular 3D reconstruction approach, named GP-Recon, to perform high-fidelity online neural 3D reconstruction with fine-grained geometric details. We incorporate geometric prior (GP) into a scene's neural geometry learning to better capture its geometric details and, more importantly, propose an online volume rendering optimization to reconstruct and maintain geometric details during the online reconstruction task. The extensive comparisons with state-of-the-art approaches show that our GP-Recon consistently generates more accurate and complete reconstruction results with much better fine-grained details, both quantitatively and qualitatively.

An overview of Melanommataceae (Pleosporales, Dothideomycetes): Current insight into the host associations and geographical distribution with some interesting novel additions from plant litter.

Melanommataceous species exhibit high diversity with a cosmopolitan distribution worldwide and show a prominent saprobic lifestyle. In this study, we explored five saprobic species collected from plant litter substrates from terrestrial habitats in China and Thailand. A combination of morphological characteristics and multi-locus phylogenetic analyses was used to determine their taxonomic classifications. Maximum Likelihood and Bayesian Inference analyses of combined LSU, SSU, ITS and tef1-α sequence data were used to clarify the phylogenetic affinities of the species. Byssosphaeriapoaceicola and Herpotrichiazingiberacearum are introduced as new species, while three new host records, Bertiellafici, By.siamensis and Melanommapopulicola are also reported from litter of Cinnamomumverum, Citrustrifoliata and Fagussylvatica, respectively. Yet, despite the rising interest in the melanommataceous species, there is a considerable gap in knowledge on their host associations and geographical distributions. Consequently, we compiled the host-species associations and geographical distributions of all the so far known melanommataceous species.

A new method for synthesizing terminal olefins from esters using the Corey-Chaykovsky reagent.

A new method for the synthesis of terminal olefins was developed through the reaction of the Corey-Chaykovsky reagent (dimethyl-sulfonium methylide) with readily available esters. After the domino process of nucleophilic addition, elimination and rearrangement in one pot, the terminal olefins were synthesized in high yields (up to 84%) under mild conditions. The synthetic method was well tolerated by many functional groups and a new route for the synthesis of various terminal olefin derivatives is provided. In the end, a possible reaction mechanism is proposed, which is supported by DFT calculations.

Recyclable V2O5/g-C3N4 Heterojunction-Catalyzed Visible-Light-Promoted C3-H Trifluoromethylation of Quinoxalin-2-(1H)-ones.

A visible-light-initiated C-H trifluoromethylation of quinoxalin-2(1H)-ones was established using a Z-scheme V2O5/g-C3N4 heterojunction as a recyclable photocatalyst in an inert atmosphere at room temperature under additive-free and mild conditions. A variety of trifluoromethylated quinoxalin-2-(1H)-one derivatives were heterogeneously generated in moderate to high yields, exhibiting good functional group tolerance. Remarkably, the recyclable V2O5/g-C3N4 catalyst could be reused five times with a slight loss of catalytic activity.

Satisfactory Tensile Strength and Strain of Recyclable Polyurethane with a Trimaleimide Structure for Thermal Self-Healing and Anticorrosive Coatings.

Bismaleimide (BMI) is often used as the cross-linking reagent in Diels-Alder (D-A)-type intrinsic self-healing materials (DISMs) to promote the connectivity of damaged surfaces based on reversible D-A bond formation on the molecular scale. Until now, although DISMs have exhibited great potential in the applications of various sensors, electronic skin, and artificial muscles, it is still difficult to prepare DISMs with satisfactory self-healing abilities and high tensile strengths and strains at the same time, thus largely limiting their applications in self-healing anticorrosive coatings. Herein, symmetrical trimaleimide (TMI) was successfully synthesized, and trimaleimide-structured D-A self-healing polyurethane (TMI-DA-PU) was prepared via the reversible D-A reaction (cycloaddition of furan and maleimide). As a DISM, TMI-DA-PU exhibits apparently higher self-healing efficiency (98.7%), tensile strength (25.4 MPa), and strain (1378%) compared to bismaleimide-structured D-A self-healing polyurethane (BMI-DA-PU) (self-healing efficiency, 90.2%; tensile strength, 19.3 MPa; strain, 1174%). In addition, TMI-DA-PU shows a high recycling efficiency (>95%) after 4 cycles of recycling. A series of characterizations indicate that TMI provides more monoene rings as the self-healing sites, forms denser cross-linked structures compared to BMI, and is, thus, more appropriate to be used for DISM applications. Moreover, the barrier abilities of coatings can be semi-quantitatively expressed by the impedance value at 0.01 Hz (|Z|0.01 Hz). The |Z|0.01 Hz value of the TMI-DA-PU coating is 3.93 × 109 Ω cm2 on day 0, which is significantly higher than that of the BMI-DA-PU coating (6.76 × 108 Ω cm2 on day 0), indicating that the denser rigid cross-linked structure of TMI results in the small porosity in the TMI-DA-PU coating, thus effectively improving the anticorrosion performance. The construction of DISMs with the structure of TMI demonstrates immense potential in self-healing anticorrosive coatings.

A review of spatial distribution of typical antibiotic resistance genes in marine environment surrounding China.

Antibiotic resistance genes (ARGs) have been steadily increasing due to the extensive overuse of antibiotics in the marine environment. Currently, the research considering ARGs distribution in marine ecosystems gains more interest. As the coastal sea has been regarded as one of the most polluted areas by antibiotic contaminants in China. However, no comprehensive review of the spatial distribution of ARGs in marine environment surrounding China. The main objective of this review is to investigate the level, characteristic, and spatial distribution of ARGs in the marine environment (seawater and sediments) surrounding China. Key sea areas, such as Bohai Sea, Yellow Sea, East China Sea, and South China Sea were selected in this review. The marine environment was the reservoir of ARGs, and ARGs in seawater were generally 1 to 2 orders of magnitude higher than that in sediments. Total ARGs were more abundant in the Yellow Sea, followed by the Bohai Sea, the East China Sea, and the South China Sea. This study raises questions regarding the spread and distribution for antibiotic resistance in marine environments.

Photoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN) for cross-modal individual analysis of the whole brain.

Cross-modal analysis of the same whole brain is an ideal strategy to uncover brain function and dysfunction. However, it remains challenging due to the slow speed and destructiveness of traditional whole-brain optical imaging techniques. Here we develop a new platform, termed Photoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN), for non-destructive, high-speed, 3D imaging of ex vivo rodent, ferret, and non-human primate brains. Using an optimally designed image acquisition scheme and an accompanying machine-learning algorithm, PATTERN extracts signals of genetically-encoded probes from photobleaching-based temporal modulation and enables reliable visualization of neural projection in the whole central nervous system with 3D isotropic resolution. Without structural and biological perturbation to the sample, PATTERN can be combined with other whole-brain imaging modalities to acquire the whole-brain image with both high resolution and morphological fidelity. Furthermore, cross-modal transcriptome analysis of an individual brain is achieved by PATTERN imaging. Together, PATTERN provides a compatible and versatile strategy for brain-wide cross-modal analysis at the individual level.