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Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer and presents clinically with a high degree of biological heterogeneity and distinct clinical outcomes. The current paradigm of LUAD etiology posits alveolar epithelial type II (AT2) cells as the primary cell of origin, while the role of AT1 cells in LUAD oncogenesis remains unknown. Here, we examine oncogenic transformation in mouse Gram-domain containing 2 (Gramd2)+ AT1 cells via oncogenic KRASG12D. Activation of KRASG12D in AT1 cells induces multifocal LUAD, primarily of papillary histology. Furthermore, KRT8+ intermediate cell states were observed in both AT2- and AT1-derived LUAD, but SCGB3A2+, another intermediate cell marker, was primarily associated with AT1 cells, suggesting different mechanisms of tumor evolution. Collectively, our study reveals that Gramd2+ AT1 cells can serve as a cell of origin for LUAD and suggests that distinct subtypes of LUAD based on cell of origin be considered in the development of therapeutics.

Abstract Background Angiostrongyliasis is a zoonotic parasitic disease caused by the rat lungworm Angiostrongylus cantonensis. The intermediate hosts of A. cantonensis are gastropods, and snail species such as Pomacea canaliculata play a key role in the transmission of human angiostrongyliasis. Detecting A. cantonensis infection in snails is an important component of epidemiological surveillance and the control of angiostrongyliasis. Methods In this study, a new method for diagnosing A. cantonensis infection in gastropods was developed by recovering larvae from the buccal cavity of three snail species. The entire buccal cavity of a snail was extracted, and the tissue was pressed between two microscope slides to observe whether A. cantonensis larvae were present. Our new method was compared with traditional pathogenic detection methods of lung microscopy, tissue homogenization, and artificial digestion. We artificially infected 160 P. canaliculata, 160 Cipangopaludina chinensis, and 160 Bellamya aeruginosa snails with A. cantonensis. Then, the four different detection methods were used to diagnose infection in each snail species at 7, 14, 21, and 28 days post exposure. Results We found no significant difference in the percentages of infected P. canaliculata snails using the four methods to detect A. cantonensis larvae. The radula pressing method had a mean detection rate of 80%, while the lung microscopy (81.3%), tissue homogenization (83.8%), and artificial digestion (85%) methods had slightly greater detection rates. Similarly, the percentages of infected C. chinensis snails that were detected using the radula pressing (80%), tissue homogenization (82.1%), and artificial digestion (83.8%) methods were not significantly different. Finally, the percentages of infected B. aeruginosa snails that were detected using the radula pressing (81.3%), tissue homogenization (81.9%), and artificial digestion (81.4%) methods were not significantly different. These results showed that the radula pressing method had a similar detection rate to traditional lung microscopy, tissue homogenization, or artificial digestion methods. Conclusions This study demonstrates a new method for the qualitative screening of gastropods that act as intermediate hosts of A. cantonensis (and other Angiostrongylus species), provides technical support for the control of human angiostrongyliasis, and furthers research on A. cantonensis. Graphical Abstract

The all-vanadium redox flow technology has garnered significant attention in the energy storage field, due to its attributes of high safety, high reliability, environmental friendliness, and power-capacity decoupling. Within all-vanadium redox flow energy storage setups, the control system is deemed the core, evolving towards enhanced integration, precision, and intelligence. This paper seeks to elevate these benchmarks and advance technological levels in the localization of this system. Based on a review of technologies related to the entire control system, this study conducted an in-depth analysis concerning key parameters and control logic. Addressing some key concerns within the control system, solutions were proposed, including temperature control, operational modes, and state-of-charge (SOC) estimation. The subsequent study focused on designing architecture for monitoring and managing all-vanadium redox flow energy storage systems through a modular approach, aiming at a more adaptable, elastic, and scalable control system. Furthermore, the developed control system was verified through practical implementation in commercial energy storage and applications under grid-connected environments. Based on the study outcomes, this paper also explores potential future technological trends for all-vanadium redox flow energy storage control systems in various aspects such as operation, maintenance, losses, and equilibrium.

The surge in urbanization has correspondingly given rise to exacerbated carbon footprint and burgeoning heavy metal (HM) contamination, constituting a critical impediment to the realization of environmentally sustainable urban development pathways. Therefore, it is highly essential to investigate the impacts of urbanization process on soil carbon, heavy metals (HMs), as well as their interrelationships. Employing remote sensing and land use data within a 45 km radius in Chongqing, this study selected 31 sites to assess the variation in urban green spaces (UGSs) carbon sequestration capabilities and associated HM pollution risks across differing urbanization levels. Results showed that urbanization dynamics and land use history play a more decisive role than current anthropogenic management in shaping the distribution of soil carbon and HMs within urban environments. The average soil organic carbon (SOC) distribution of UGSs is 8.47 mg ha−1 (1.50–24.20 mg ha−1), concurrent with moderate HM pollution showing Ni: 32.03–33.50 mg kg−1, Pb: 27.93–29.65 mg kg−1, Cu: 26.97–41.20 mg kg−1, while Cd exhibits the most severe pollution range of 0.23–0.30 mg kg−1. The rate of urbanization significantly influences SOC stocks, exhibiting an increase when the urbanization rate is below 70.79 % and a decrease upon surpassing this threshold. The concentration of HMs is predominantly determined by the historical usage of the land, with a marked escalation correlating with the duration of land utilization history. These relationships were quantitatively modeled through the application of fitted linear functions. The structural equation model demonstrated that UGSs operating without anthropogenic disturbance tend towards degradation, indicating that temporary homeostasis might be sustained via the addition of N and P nutrients and pH modulation. In conclusion, we formulate an Urban Green Spaces Development Hypothesis that aims to shed light on the multifaceted challenges encountered by cities amidst varying degrees of urbanization and, concurrently, to probe potential ameliorative strategies.

Non-small cell lung cancer (NSCLC) is the main type of lung cancer, accounting for 85% to 90% of cases. The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has greatly improved the prognosis of NSCLC patients. However, with prolonged drug use, the inevitable occurrence of acquired resistance leads to disease recurrence, progression, and even patient's death. Metabolic reprogramming is one of the hallmarks of malignant tumors and refers to metabolic changes in tumor cells to meet energy needs. In various cancers, lipid synthesis, distribution, and catabolism of tumor cells are altered to adapt to the lack of nutrients and oxygen in the tumor microenvironment. This paper focuses on how lipid metabolism reprogramming in NSCLC leads to resistance to EGFR-TKIs and how modulation of lipid metabolism increases the sensitivity of NSCLC to EGFR-TKIs. It summarizes and consolidates existing research progress to provide a reference for basic research and clinical treatment of EGFR-TKIs resistance in NSCLC.

Objective To investigate the efficacy and safety of traditional AG regimen [gemcitabine （1 000 mg/m, d1, d8） + albumin-bound paclitaxel（125 mg/m, d1, d8）, 21 days as a cycle] and other gemcitabine-based regimen [gemcitabine alone or combined with S-1（tegafur, gimeracil and oteracil potassium）/oxaliplatin/arotinib] in the treatment of advanced and metastatic pancreatic cancer. Methods From January 2017 to January 2022, 64 patients with advanced and metastatic pancreatic cancer were retrospectively collected from Sir Run Run Hospital of Nanjing Medical University. There were 33 patients received traditional AG therapy and 31 patients received chemotherapy mainly with gemcitabine. Survival analysis was conducted based on follow-up data, with the study endpoints being overall survival (OS） and progression free survival （PFS）, and the secondary study endpoint being the incidence of grade 3/4 adverse reactions. Results The median OS of the AG regimen group and the gemcitabine group were 12.2 months and 7.9 months, respectively, and there was no significant difference between two groups （χ=1.517, P=0.218）. The median PFS of the AG regimen group and the gemcitabine group was 7.0 months and 3.3 months, respectively（χ=8.683, P=0.003）. There was no significant difference in the incidence of grade 3/4 adverse events between the two groups of patients（P＞0.05）. Conclusion The first-line treatment of albumin-bound paclitaxel combined with gemcitabine in patients with advanced pancreatic cancer has significant clinical effects, which significantly controls the disease progress and extends the PFS of patients.

Abstract Background The current nodal (pN) classification still has limitations in stratifying the prognosis of small cell lung cancer (SCLC) patients with pathological classifications T1-2N0-2M0. Thus. This study aimed to develop and validate a modified nodal classification based on a multicenter cohort. Materials and methods We collected 1156 SCLC patients with pathological classifications T1-2N0-2M0 from the Surveillance, Epidemiology, and End Results database and a multicenter database in China. The X-tile software was conducted to determine the optimal cutoff points of the number of examined lymph nodes (ELNs) and lymph node ratio (LNR). The Kaplan-Meier method, the Log-rank test, and the Cox regression method were used in this study. We classified patients into three pathological N modification categories, new pN#1 (pN0-#ELNs > 3), new pN#2 (pN0-#ELNs ≤ 3 or pN1-2-#LNR ≤ 0.14), and new pN#3 (N1-2-#LNR > 0.14). The Akaike information criterion (AIC), Bayesian Information Criterion, and Concordance index (C-index) were used to compare the prognostic, predictive ability between the current pN classification and the new pN component. Results The new pN classification had a satisfactory effect on survival curves (Log-rank P

Abstract Introduction At present, clinical factors and hematological indicators have been proved to have great potential in predicting the prognosis of cancer patients, and no one has combined these two valuable indicators to establish a prognostic model for esophageal squamous cell carcinoma (ESCC) patients with stage T1-3N0M0 after R0 resection. To verify, we aimed to combine these potential indicators to establish a prognostic model. Methods Stage T1-3N0M0 ESCC patients from two cancer centers (including training cohort: N = 819, and an external validation cohort: N = 177)—who had undergone esophagectomy in 1995–2015 were included. We integrated significant risk factors for death events by multivariable logistic regression methods and applied them to the training cohort to build Esorisk. The parsimonious aggregate Esorisk score was calculated for each patient; the training set was divided into three prognostic risk classes according to the 33rd and 66th percentiles of the Esorisk score. The association of Esorisk with cancer-specific survival (CSS) was assessed using Cox regression analyses. Results The Esorisk model was: [10 + 0.023 × age + 0.517 × drinking history − 0.012 × hemoglobin–0.042 × albumin − 0.032 × lymph nodes]. Patients were grouped into three classes—Class A (5.14–7.26, low risk), Class B (7.27–7.70, middle risk), and Class C (7.71–9.29, high risk). In the training group, five-year CSS decreased across the categories (A: 63%; B: 52%; C: 30%, Log-rank P

The latest surveillance from the Centers for Disease Control and Prevention shows that the annual incidence of V. vulnificus infection is increasing. Unfortunately, in less well-known high-risk groups, this infection is usually excluded from differential diagnosis. Transmitted through wound exposure or ingestion, the mortality rate of foodborne diseases of V. vulnificus is the highest of all V. vulnificus. V. vulnificus is as lethal early diagnosis as Ebola and bubonic plague, so timely treatment is imperative. Sepsis caused by V. vulnificus infection mainly exists in the United States and is rarely reported in Southeast Asia. We report a 78-year-old man who went to the local hospital and complained of swelling in his right hand with severe pain. He ate raw salmon 2 days ago and denied other recognized seafood stab or trauma history and other seafood contact history. He was in septic shock at the time of treatment, so we immediately transferred to the emergency intensive care unit and tested for metagenomic next-generation sequencing (mNGS). The diagnosis was confirmed the second day after admission, and eventually he was cured and discharged from the hospital only after medical treatment, thus avoiding the risk of surgical debridement or even amputation. mNGS is helpful for early clinical diagnosis and effective early intervention for etiology, so that patients can get a good prognosis.