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Introduction: The level of atmospheric CO2 has continuously been increasing and the resulting greenhouse effects are receiving attention globally. Carbon removal from the atmosphere occurs naturally in various ecosystems. Among them, saline environments contribute significantly to the global carbon cycle. Carbonate deposits in the sediments of salt lakes are omnipresent, and the biological effects, especially driven by halophilic microalgae and bacteria, on carbonate formation remain to be elucidated. Objectives: The present study aims to characterize the carbonates formed in saline environments and demonstrate the mechanisms underlying biological-driven CO2 removal via microalgal-bacterial consortium. Methods: The carbonates naturally formed in saline environments were collected and analyzed. Two saline representative organisms, the photosynthetic microalga Dunaliella salina and its mutualistic halophilic bacteria Nesterenkonia sp. were isolated from the inhabiting saline environment and co-cultivated to study their biological effects on carbonates precipitation and isotopic composition. During this process, electrochemical parameters and Ca2+ flux, and expression of genes related to CaCO3 formation were analyzed. Genome sequencing and metagenomic analysis were conducted to provide molecular evidence. Results: The results showed that natural saline sediments are enriched with CaCO3 and enrichment of genes related to photosynthesis and ureolysis. The co-cultivation stimulated 54.54% increase in CaCO3 precipitation and significantly promoted the absorption of external CO2 by 49.63%. A pH gradient was formed between the bacteria and algae culture, creating 150.22 mV of electronic potential, which might promote Ca2+ movement toward D. salina cells. Based on the results of lab-scale induction and 13C analysis, a theoretical calculation indicates a non-negligible amount of 0.16 and 2.3 Tg C/year carbon sequestration in China and global saline lakes, respectively. Conclusion: The combined effects of these two typical representative species have contributed to the carbon sequestration in saline environments, by promoting Ca2+ influx and increase of pH via microalgal and bacterial metabolic processes.

Taking the motivation of the knowledge aggregation of age-friendly design resources as the starting point, this paper compares the development history of age-friendly design for interactive interfaces, understands the research status, hotspots, and development trend of age-friendly design for interactive interfaces from 2003 to 2022 worldwide, and summarizes and analyses them. This paper explores five aspects of aging-friendly design in the field of interactive interface design extracted from the Web of Science core collection database, including keyword co-occurrence analysis of global research literature, country/region information analysis, fundamental research areas, major research institutions, and future research directions. It explores the design methods, design trends, and design laws of aging-friendly design for interactive interfaces from a multidisciplinary perspective. The results show that: (a) Smart Home, Ambient Assisted Living (AAL), User Experience, Internet of Things (IoT), etc., are the hot topics at the forefront of interface aging design. (b) USA is the world’s leading research site for interface aging design and works closely with China, where the population aging is more serious. (c) The main research areas of interface aging are computer science and engineering ethics. (d) Udice French Research Universities, the primary publishing institution, is worth attention. (e) This review proposes three research hotspots as important development directions for interactive interface aging design, including “smart home product interaction interface aging design will become a hot topic,”“fusion of multi-source data assisted interface aging design,” and “interdisciplinary interface aging design.”

Langmuir–Blodgett (LB) film technology is an advanced technique for the preparation of ordered molecular ultra-thin films at the molecular level, which transfers a single layer of film from the air/water interface to a solid substrate for the controlled assembly of molecules. LB technology has continually evolved over the past century, revealing its potential applications across diverse fields. In this study, the latest research progress of LB film technology is reviewed, with emphasis on its latest applications in gas sensors, electrochemical devices, and bionic films. Additionally, this review evaluates the strengths and weaknesses of LB technology in the application processes and discusses the promising prospects for future application of LB technology.

With the lifestyle change, users’ demand for furniture has shown a trend for personalization and diversification. The customized furniture market is growing rapidly and gradually becoming an indispensable choice for lifestyle items. The present qualitative study sought to identify the influencing factors and relationships of user demand for customized furniture. This study constructed a 4E semi-structured interview guide, which means that interviews were conducted from 4 dimensions: essential information, information extraction, user experience, and product expectation. The interview results were coded and analyzed in combination with grounded theory. Based on the identified 38 concepts and 10 categories, we obtain 4 main categories: fundamental condition, operation behaviour, sensory value and emotional value. For the factors that affect the demand of customized furniture users, customized furniture enterprises can start from 2 levels of publicity and product design to meet user demand and improve the user purchase probability.

Abstract Background Diatoms are well known for high photosynthetic efficiency and rapid growth rate, which are not only important oceanic primary producer, but also ideal feedstock for microalgae industrialization. Their high success is mainly due to the rapid response of photosynthesis to inorganic carbon fluctuations. Thus, an in-depth understanding of the photosynthetic carbon fixation mechanism of diatoms will be of great help to microalgae-based applications. This work directed toward the analysis of whether C4 photosynthetic pathway functions in the model marine diatom Phaeodactylum tricornutum, which possesses biophysical CO2-concentrating mechanism (CCM) as well as metabolic enzymes potentially involved in C4 photosynthetic pathway. Results For P. tricornutum, differential proteome, enzyme activities and transcript abundance of carbon metabolism-related genes especially biophysical and biochemical CCM-related genes in response to different concentrations of CO2 were tracked in this study. The upregulated protein abundance of a carbonic anhydrases and a bicarbonate transporter suggested biophysical CCM activated under low CO2 (LC). The upregulation of a number of key C4-related enzymes in enzymatic activity, transcript and protein abundance under LC indicated the induction of a mitochondria-mediated CCM in P. tricornutum. Moreover, protein abundance of a number of glycolysis, tricarboxylic acid cycle, photorespiration and ornithine–urea cycle related proteins upregulated under LC, while numbers of proteins involved in the Calvin cycle and pentose phosphate pathway were downregulated. Under high CO2 (HC), protein abundance of most central carbon metabolism and photosynthesis-related proteins were upregulated. Conclusions The proteomic and biochemical responses to different concentrations of CO2 suggested multiple carbon metabolism strategies exist in P. tricornutum. Namely, LC might induce a mitochondrial-mediated C4-like CCM and the improvement of glycolysis, tricarboxylic acid cycle, photorespiration and ornithine–urea cycle activity contribute to the energy supply and carbon and nitrogen recapture in P. tricornutum to cope with the CO2 limitation, while P. tricornutum responds to the HC environment by improving photosynthesis and central carbon metabolism activity. These findings can not only provide evidences for revealing the global picture of biophysical and biochemical CCM in P. tricornutum, but also provide target genes for further microalgal strain modification to improve carbon fixation and biomass yield in algal-based industry.

Abstract Background Diatoms usually dominate phytoplankton blooms in open oceans, exhibiting extremely high population densities. Although the iron uptake rate of diatoms largely determines the magnitude and longevity of diatom blooms, the underlying mechanisms regulating iron uptake remain unclear. Results The transcription of two iron uptake proteins, ISIP2a and ISIP1, in the marine diatom Phaeodactylum tricornutum was enhanced with increasing cell density, whereas the cellular iron content showed the opposite trend. When compared with the wild-type strain, knockdown of ISIP2a resulted in 43% decrease in cellular iron content, implying the involvement of ISIP2a in iron uptake under high-cell density conditions. Incubation of the diatom cells with sonicated cell lysate conditioned by different cell densities did not affect ISIP2a and ISIP1 expression, ruling out regulation via chemical cues. In contrast, ISIP2a and ISIP1 transcription were strongly induced by red light. Besides, chlorophyll fluorescence excited from the blue light was also positively correlated with population density. Subsequently, a “sandwich” illumination incubator was designed to filter out stray light and ensure that the inner layer cells only receive the emitted chlorophyll fluorescence from outer layers, and the results showed that the increase in outer cell density significantly elevated ISIP2a and ISIP1 transcription in inner layer cells. In situ evidence from Tara oceans also showed positively correlated between diatom ISIP transcripts and chlorophyll content. Conclusions This study shows that chlorophyll fluorescence derived from neighboring cells is able to upregulate ISIP2a and ISIP1 expression to facilitate iron assimilation under high-cell density. These results provide novel insights into biotic signal sensing in phytoplankton, which can help to elucidate the underlying mechanisms of marine diatom blooms.

Abstract Background Diatoms contribute 20% of the global primary production and are adaptable in dynamic environments. Diatoms always bloom earlier in the annual phytoplankton succession instead of dinoflagellates. However, how diatoms acclimate to a dynamic environment, especially under changing light conditions, remains unclear. Results We compared the growth and photosynthesis under fluctuating light conditions of red tide diatom Skeletonema costatum, red tide dinoflagellate Amphidinium carterae, Prorocentrum donghaiense, Karenia mikimotoi, model diatom Phaeodactylum tricornutum, Thalassiosira pseudonana and model dinoflagellate Dinophycae Symbiodinium. Diatoms grew faster and maintained a consistently higher level of photosynthesis. Diatoms were sensitive to the specific inhibitor of Proton Gradient Regulation 5 (PGR5) depending photosynthetic electron flow, which is a crucial mechanism to protect their photosynthetic apparatus under fluctuating light. In contrast, the dinoflagellates were not sensitive to this inhibitor. Therefore, we investigate how PGR5 functions under light fluctuations in the model diatom P. tricornutum by knocking down and overexpressing PGR5. Overexpression of PGR5 reduced the photosystem I acceptor side limitation (Y (NA)) and increased growth rate under severely fluctuating light in contrast to the knockdown of PGR5. Conclusion Diatoms acclimatize to fluctuating light conditions better than dinoflagellates. PGR5 in diatoms can regulate their photosynthetic electron flow and accelerate their growth under severe light fluctuation, supporting fast biomass accumulation under dynamic environments in pioneer blooms.

The upregulation of heat shock protein 70 (hsp70) gene under high temperature stress is a common phenomenon. Although heat shock protein-mediated stress responses play an important role in intertidal Neopyropia yezoensis, the detailed regulatory mechanism of the hsp70 gene expression is still unclear. Here, a full-length sequence of the hsp70-2 gene was cloned and its’ expression regulation was analyzed. There was an activating transcription factors element (ATFE) of cAMP-dependent protein kinase (PKA) was found at the gene promoter region and a highly conserved deduced amino acid sequence with calmodulin-binding activity was detected. Reagents implicated in the induction of the hsp70 gene were then selected to treat the algal samples at 24°C, and the photosynthetic parameters, transcription and translation of this gene were determined. Results showed that quercetin inhibited the transcription of the hsp70-2 gene, significantly decreased the synthesis of the HSP70-2 protein, and lowered the photosynthetic activity of N. yezoensis under high temperature stress conditions. Although the addition of trifluoperazine (TFP), an inhibitor of calmodulin (CAM), downregulated the photosynthetic parameters, the transcription of the hsp70-2 gene was not influenced at high temperature treatment, implying that CAM was not involved in the transcription of the hsp70-2 gene but involved in the heat stress reponding pathways. 5′-aminoimidasole-4-carboxamide-1-β-d-ribofuranoside (AICAR) promoted the synthesis of hsp70-2 transcripts significantly and HSP70-2 protein slightly, which indicated that AMPK regulated the induction of the hsp70-2 gene in N. yezoensis. Forskolin also promoted the upregulation of the hsp70-2 gene. Thus, both AMPK and cAMP-dependent protein kinase (PKA) could phosphorylate HSF and activate the expression of the hsp70-2 gene in N. yezoensis. However, there was no strict correlation between transcripts of the hsp70-2 gene and HSP70-2 protein contents. It was proposed that the posttranscriptional mechanisms were involved in regulating the synthesis of the HSP70-2 protein. Which allowed it to adapt to the extremely variable intertidal environments with an instant responding manner, since the accumulated transcripts could be translated rapidly when needed.

Abscisic acid (ABA) is regarded as crucial for plant adaptation to water-limited conditions and it functions evolutionarily conserved. Thus, insights into the synthesis of ABA and its regulation on downstream stress-responsive genes in Neopyropia yezoensis, a typical Archaeplastida distributed in intertidal zone, will improve the knowledge about how ABA signaling evolved in plants. Here, the variations in ABA contents, antioxidant enzyme activities and expression of the target genes were determined under the presence of exogenous ABA and two specific inhibitors of the ABA precursor synthesis. ABA content was down-regulated under the treatments of each or the combination of the two inhibitors. Antioxidant enzyme activities like SOD, CAT and APX were decreased slightly with inhibitors, but up-regulated when the addition of exogenous ABA. The quantitative assays using real-time PCR (qRT-PCR) results were consistent with the enzyme activities. All the results suggested that ABA can also alleviate oxidative stress in N. yezoensis as it in terrestrial plant. Combined with the transcriptome assay, it was hypothesized that ABA is synthesized in N. yezoensis via a pathway that is similar to the carotenoid pathway in higher plants, and both the MVA and that the MEP pathways for isoprenyl pyrophosphate (IPP) synthesis likely exist simultaneously. The ABA signaling pathway in N. yezoensis was also analyzed from an evolutionary standpoint and it was illustrated that the emergence of the ABA signaling pathway in this alga is an ancestral one. In addition, the presence of the ABRE motif in the promoter region of antioxidase genes suggested that the antioxidase system is regulated by the ABA signaling pathway.

Abstract Background Numerous studies have shown that stress induction and genetic engineering can effectively increase lipid accumulation, but lead to a decrease of growth in the majority of microalgae. We previously found that elevated CO2 concentration increased lipid productivity as well as growth in Phaeodactylum tricornutum, along with an enhancement of the oxidative pentose phosphate pathway (OPPP) activity. The purpose of this work directed toward the verification of the critical role of glucose-6-phosphate dehydrogenase (G6PDH), the rate-limiting enzyme in the OPPP, in lipid accumulation in P. tricornutum and its simultaneous rapid growth rate under high-CO2 (0.15%) cultivation. Results In this study, G6PDH was identified as a target for algal strain improvement, wherein G6PDH gene was successfully overexpressed and antisense knockdown in P. tricornutum, and systematic comparisons of the photosynthesis performance, algal growth, lipid content, fatty acid profiles, NADPH production, G6PDH activity and transcriptional abundance were performed. The results showed that, due to the enhanced G6PDH activity, transcriptional abundance and NAPDH production, overexpression of G6PDH accompanied by high-CO2 cultivation resulted in a much higher of both lipid content and growth in P. tricornutum, while knockdown of G6PDH greatly decreased algal growth as well as lipid accumulation. In addition, the total proportions of saturated and unsaturated fatty acid, especially the polyunsaturated fatty acid eicosapentaenoic acid (EPA; C20:5, n-3), were highly increased in high-CO2 cultivated G6PDH overexpressed strains. Conclusions The successful of overexpression and antisense knockdown of G6PDH well demonstrated the positive influence of G6PDH on algal growth and lipid accumulation in P. tricornutum. The improvement of algal growth, lipid content as well as polyunsaturated fatty acids in high-CO2 cultivated G6PDH overexpressed P. tricornutum suggested this G6PDH overexpression-high CO2 cultivation pattern provides an efficient and economical route for algal strain improvement to develop algal-based biodiesel production.

Abstract Background Increasing CO2 emissions have resulted in ocean acidification, affecting marine plant photosynthesis and changing the nutrient composition of marine ecosystems. The physiological and biochemical processes of marine phytoplankton in response to ocean acidification have been reported, but have been mainly focused on growth and photosynthetic physiology. To acquire a thorough knowledge of the molecular regulation mechanisms, model species with clear genetic background should be selected for systematic study. Phaeodactylum tricornutum is a pennate diatom with the characteristics of small genome size, short generation cycle, and easy to transform. Furthermore, the genome of P. tricornutum has been completely sequenced. Results and discussion In this study, P. tricornutum was cultured at high and normal CO2 concentrations. Cell composition changes during culture time were investigated. The 13C isotope tracing technique was used to determine fractional labeling enrichments for the main cellular components. The results suggested that when lipid content increased significantly under high CO2 conditions, total protein and soluble sugar contents decreased. The 13C labeling experiment indicated that the C skeleton needed for fatty acid C chain elongation in lipid synthesis under high CO2 conditions is not mainly derived from NaHCO3 (carbon fixed by photosynthesis). Conclusion This study indicated that breakdown of intracellular protein and soluble sugar provide C skeleton for lipid synthesis under high CO2 concentration.

Cyanobacteria are rich in phytochemicals, which have beneficial impacts on the prevention of many diseases. This study aimed to comprehensively characterize phytochemicals and evaluate multifunctional bioactivities in the ethanolic extract of the cyanobacterium Leptolyngbya sp. KC45. Results found that the extract mainly contained chlorophylls, carotenoids, phenolics, and flavonoids. Through LC–ESI–QTOF–MS/MS analysis, 38 phenolic compounds with promising bioactivities were discovered, and a higher diversity of flavonoids was found among the phenolic compounds identified. The extract effectively absorbed the harmful UV rays and showed high antioxidant activity on DPPH, ABTS, and PFRAP. The extract yielded high-efficiency inhibitory effects on enzymes (tyrosinase, collagenase, ACE, and α-glucosidase) related to diseases. Interestingly, the extract showed a strong cytotoxic effect on cancer cells (skin A375, lung A549, and colon Caco-2), but had a much smaller effect on normal cells, indicating a satisfactory level of safety for the extract. More importantly, the combination of the DNA ladder assay and the TUNEL assay proved the appearance of DNA fragmentation in cancer cells after a 48 h treatment with the extract, confirming the apoptosis mechanisms. Our findings suggest that cyanobacterium extract could be potentially used as a functional ingredient for various industrial applications in foods, cosmetics, pharmaceuticals, and nutraceuticals.

Digestive system cancers (DSC) are the most common cancers worldwide and often associated with poor prognosis because of their characteristics of invasive and metastatic. Thus, it is particularly necessary to find novel molecular targets for early diagnosis, as well as targeted treatment of DSC. B7-H3, which was previously referred to as a modulatory ligand that regulate T-cell-mediated immune reaction, is a B7-family member of co-stimulatory biomolecules, and in recent years it was found that its concentration was remarkably up modulated in serum, as well as tissues of DSC patients. Numerous studies have documented that B7-H3 has a vital function in the DSC. Herein, we summarize the current literature on diagnosis and prognosis potential of B7-H3 in DSC including those of the esophagus, gastric, liver, pancreas, and colon.

Pyropia yezoensis can survive the severe water loss that occurs during low tide, making it an ideal species to investigate the acclimation mechanism of intertidal seaweed to special extreme environments. In this study, we determined the effects of high salinity on photosynthesis using increasing salinity around algal tissues. Both electron transport rates, ETR (I) and ETR (II), showed continuous decreases as the salinity increased. However, the difference between these factors remained relatively stable, similar to the control. Inhibitor experiments illustrated that there were at least three different cyclic electron transport pathways. Under conditions of severe salinity, NAD(P)H could be exploited as an endogenous electron donor to reduce the plastoquinone pool in Py. yezoensis. Based on these findings, we next examined how these different cyclic electron transport (CETs) pathways were coordinated by cloning the gene (HM370553) for ferredoxin-NADP+ oxidoreductase (FNR). A phylogenetic tree was constructed, and the evolutionary relationships among different FNRs were evaluated. The results indicated that the Py. yezoensis FNR showed a closer relationship with cyanobacterial FNR. The results of both real-time polymerase chain reaction and western blotting showed that the enzyme was upregulated under 90–120‰ salinity. Due to the structure-function correlations in organism, Py. yezoensis FNR was proposed to be involved in NAD(P)H-dependent Fd+ reduction under severe salinity conditions. Thus, through the connection between different donors bridged by FNR, electrons were channeled toward distinct routes according to the different metabolic demands. This was expected to make the electron transfer in the chloroplasts become more flexible and to contribute greatly to acclimation of Py. yezoensis to the extreme variable environments in the intertidal zone.

The xanthophyll cycle (Xc), which involves violaxanthin de-epoxidase (VDE) and the zeaxanthin epoxidase (ZEP), is one of the most rapid and efficient responses of plant and algae to high irradiance. High light intensity can activate VDE to convert violaxanthin (Vx) to zeaxanthin (Zx) via antheraxanthin (Ax). However, it remains unclear whether VDE remains active under low light or dark conditions when there is no significant accumulation of Ax and Zx, and if so, how the ΔpH required for activation of VDE is built. In this study, we used salicylaldoxime (SA) to inhibit ZEP activity in the intertidal macro-algae Ulva sp. (Ulvales, Chlorophyta) and then characterized VDE under low light and dark conditions with various metabolic inhibitors. With inhibition of ZEP by SA, VDE remained active under low light and dark conditions, as indicated by large accumulations of Ax and Zx at the expense of Vx. When PSII-mediated linear electron transport systems were completely inhibited by SA and DCMU, alternative electron transport systems (i.e., cyclic electron transport and chlororespiration) could maintain VDE activity. Furthermore, accumulations of Ax and Zx decreased significantly when SA, DCMU, or DBMIB together with an inhibitor of chlororespiration (i.e., propyl gallate (PG)) were applied to Ulva sp. This result suggests that chlororespiration not only participates in the build-up of the necessary ΔpH, but that it also possibly influences VDE activity indirectly by diminishing the oxygen level in the chloroplast.

Both biomass dominated green vegetative cells (GV) and astaxanthin-dominated orange resting cells (OR) affect the final astaxanthin yield in industry. Examination of Haematococcus pluvialis revealed that the OR cells greatly varied from the GV cells at both cellular and subcellular levels. In particular, the thylakoid membranes in the OR were disassembled and fragmented. Furthermore, the OR conserved most of the photosynthetic pigments, with elevated concentrations of violaxanthin, antheraxanthin, and neoxanthin. Notably, moderate photosynthesis was detected in OR, even though most of the thylakoid membranes were disassembled, when compared with those in the GV. However, the energy distribution pattern between photosystem I and II (PSI and PSII) in the OR favored PSI, which was also confirmed by 77-K fluorescence. As zeaxanthin was not detected in the OR, we attribute the acclimation role to astaxanthin, instead of xanthophyll cycle. Additionally, proteomic-scale comparison analysis of thylakoids of the OR and GV indicated no photosynthetically remarkable variations. However, an extensive acclimation mechanism of H. pluvialis was proposed, in which proteins in thylakoid of GV were noted to be involved in biomass accumulation and those in OR were involved in stress response. Conclusions of the comparative analysis might provide some physiological background of OR for astaxanthin production by using H. pluvialis.

For plants and algae, exposure to high light levels is deleterious to their photosynthetic machineries. It also can accelerate water evaporation and thus potentially lead to drought stress. Most photosynthetic organisms protect themselves against high light caused photodamages by xanthophyll cycle-dependent thermal energy dissipation. It is generally accepted that high light activates xanthophyll cycle. However, the relationship between xanthophyll cycle and drought stress remains ambiguous. Herein, Ulva pertusa (Chlorophyta), a representative perennial intertidal macro-algae species with high drought-tolerant capabilities and simple structures, was used to investigate the operation of xanthophyll cycle during desiccation in air. The results indicate that desiccation under dim light induced accumulation of antheraxanthin (Ax) and zeaxanthin (Zx) at the expense of violaxanthin (Vx). This accumulation could be arrested by dithiothreitol completely and by uncoupler (carbonyl cyanide p-trifluoromethoxyphenylhydrazone) partially, implying the participation of Vx de-epoxidase in conversion of Vx to Ax and Zx. Treatment with inhibitors of electron transport along thylakoid membrane, e.g. DCMU, PG and DBMIB, did not significantly arrest desiccation-induced accumulation of Ax and Zx. We propose that for U. pertusa, besides excess light, desiccation itself could also induce accumulation of Ax and Zx. This accumulation could proceed without electron transport along thylakoid membrane, and is possibly resulting from the reduction of thylakoid lumen volume during desiccation. Considering the pleiotropic effects of Ax and Zx, accumulated Ax and Zx may function in protecting thylakoid membrane and enhancing thermal quenching during emersion in air.

Abstract Chemo-immunotherapy is the current first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC), but survival benefits are modest. We aimed to evaluate the safety, antitumor activity and biomarkers of first-line camrelizumab and apatinib plus chemotherapy in untreated ES-SCLC patients. In this single-arm trial (ClinicalTrials.gov NCT05001412), eligible patients received 2 cycles of etoposide and carboplatin (EC) as induction treatment followed by 2–4 cycles of camrelizumab, apatinib plus EC, then maintenance camrelizumab plus apatinib. Primary endpoint was safety. Secondary endpoints included objective response rate (ORR), duration of response, progression-free survival (PFS), and overall survival (OS). Targeted sequencing and whole transcriptome sequencing were performed to explore biomarkers. All enrolled 40 patients were treated and analyzed for safety. During the entire treatment, treatment-emergent adverse events (TEAEs) occurred in 40 patients (100%), and 30 (75.0%) were grade ≥3. The most common grade ≥3 TEAEs were neutropenia (35.0%), anemia (15.0%) and increased alanine aminotransferase (15.0%). No treatment-related deaths occurred. Among 36 evaluable patients, ORR was 88.9% (95% CI: 73.9%–96.9%), median PFS was 7.3 months (95% CI: 6.6–9.2) and median OS was 17.3 months (11.8-not reached). Mutations in RB1, high levels of tumor mutation burden, natural killer cells, and interferons, and low levels of cancer-associated fibroblasts, correlated with prolonged PFS. Induction chemotherapy followed by camrelizumab, apatinib plus EC demonstrated acceptable safety and promising antitumor activity in untreated ES-SCLC patients. The identified biomarkers need further validation. Trial Registration ClinicalTrials.gov Identifier: NCT05001412.

Abstract Purpose Conventional radiotherapy (CRT) has limited local control and poses a high risk of severe toxicity in large lung tumors. This study aimed to develop an integrated treatment plan that combines CRT with lattice boost radiotherapy (LRT) and monitors its dosimetric characteristics. Methods This study employed cone-beam computed tomography from 115 lung cancer patients to develop a U-Net + + deep learning model for generating synthetic CT (sCT). The clinical feasibility of sCT was thoroughly evaluated in terms of image clarity, Hounsfield Unit (HU) consistency, and computational accuracy. For large lung tumors, accumulated doses to the gross tumor volume (GTV) and organs at risk (OARs) during 20 fractions of CRT were precisely monitored using matrices derived from the deformable registration of sCT and planning CT (pCT). Additionally, for patients with minimal tumor shrinkage during CRT, an sCT-based adaptive LRT boost plan was introduced, with its dosimetric properties, treatment safety in high dose regions, and delivery accuracy quantitatively assessed. Results The image quality and HU consistency of sCT improved significantly, with dose deviations ranging from 0.15% to 1.25%. These results indicated that sCT is feasible for inter-fraction dose monitoring and adaptive planning. After rigid and hybrid deformable registration of sCT and pCT, the mean distance-to-agreement was 0.80 ± 0.18 mm, and the mean Dice similarity coefficient was 0.97 ± 0.01. Monitoring dose accumulation over 20 CRT fractions showed an increase in high-dose regions of the GTV (P

Abstract As a medium to understand the nature of glass transition, ultrastable glasses have garnered increasing attention for their significance in fundamental science and technological applications. Most studies have produced ultrastable glasses through a surface-controlled process using physical vapor deposition. Here, we demonstrate an approach to accessing ultrastable glasses via the glass-to-glass transition, a bulk transformation that is inherently free from size constraints and anisotropy. The resulting ultrastable glass exhibits a significantly enhanced density (improved by 2.3%), along with high thermodynamic, kinetic, and mechanical stability. Furthermore, we propose that this method of accessing ultrastable glasses is general for metallic glasses, based on the examination of the competitive relationship between the glass-to-glass transition and crystallization. This strategy is expected to facilitate the proliferation of the ultrastable glass family, helping to resolve the instability issues of glass materials and devices and deepen our understanding of glasses and the glass transition.

Abstract Objective The aim of this study is to explore the clinicopathological features, radiographic manifestations, treatment options, and prognosis of primary pulmonary angiosarcoma (PPAS). Method We summarized and analyzed the clinical data of 11 patients with primary pulmonary angiosarcoma treated at the First Affiliated Hospital of Guangzhou Medical University between January 2018 and January 2024. A retrospective analysis was conducted in conjunction with a review of the relevant literature. Results Among the 11 cases, the primary symptoms were nonspecific respiratory issues, with chest pain, cough, and shortness of breath being the most common. Initial diagnosis was correct in only 2 cases, while the remaining 9 cases were misdiagnosed as other conditions, such as lung nodules, infections, or pulmonary embolism. All patients were ultimately diagnosed via pathology, with CD31 and CD34 showing a high positivity rate of 60%. Of the 11 patients, 9 have died, and 2 remain alive. The average survival period was 13.2 months.Based on the number of lesions, PPAS was categorized into three types: solitary, multiple, and invasive pulmonary artery. The average survival period for the solitary type (2 cases) was 15.5 months, for the multiple type (5 cases) was 6.6 months, and for the pulmonary artery type (4 cases) was 20.5 months. Among the 3 patients who underwent surgery, the median overall survival (OS) was 23.0 months, whereas for the 8 non-surgical patients, the median OS was 9.7 months. Conclusion Primary pulmonary angiosarcoma is a rare, highly aggressive vascular malignancy characterized by nonspecific clinical symptoms and a tendency for metastasis and pulmonary artery embolism. Currently, no effective treatment exists, and the overall prognosis is poor.

Abstract Background Immune checkpoint inhibitor-related pneumonitis (CIP) stands out as a particularly severe adverse event caused by immune checkpoint inhibitors, with a substantial real-world incidence ranging from 13 to 19%. While systemic corticosteroids represent the standard treatment for CIP, therapeutic options become limited in cases where patients do not respond to corticosteroid therapy. Such patients are classified as having steroid-resistant CIP, often associated with a poor prognosis. This case study provides insight into the symptoms, diagnostic process, and treatment approach for steroid-resistant CIP. Notably, successful management is demonstrated through the utilization of cyclosporine, highlighting its potential mechanisms of action in effectively treating steroid-resistant CIP. Case description We present the case of a 53-year-old male with stage IV. A non-small cell lung cancer (NSCLC), who experienced elevated fever, cough, and dyspnea subsequent to immunotherapy treatment. Based on his medical history, clinical manifestations, and radiological findings, the patient was diagnosed with CIP. Initial administration of led to improvement, but during the subsequent tapering of corticosteroid therapy, a resurgence of CIP occurred, resulting in respiratory failure. Consequently, we arrived at the diagnosis of steroid-resistant CIP, prompting the implementation of a combination therapy with cyclosporine and corticosteroids to establish stable disease control. Upon systematic reduction of corticosteroid dosage, the patient maintained a favorable response with no recurrence. Conclusions This marks the first instance of effectively managing steroid-resistant CIP through the combined use of cyclosporine and corticosteroids. Presently, cases of steroid-resistant CIP remain infrequent, necessitating vigilant and meticulous monitoring within clinical settings. Notably, there exists no distinct guideline specifying a singular agent for rescuing patients unresponsive to corticosteroid therapy. Therefore, cyclosporine emerges as a promising and efficacious treatment alternative for individuals unresponsive to corticosteroid intervention in the context of CIP.

Abstract With the establishment of “Dual Carbon” targets and industrial restructuring in China, the transition from the secondary industry to the tertiary industry has facilitated the rapid development of the financial sector. However, the significant CO2 emissions embodied within inter-provincial trade result in carbon leakage, posing challenges in assigning equitable carbon reduction responsibilities to the financial sectors across the 31 provinces of China. This study establishes a framework for evaluating CO2 emissions of financial sectors through 134 samples of 60 listed financial enterprises in the 31 provinces, tracking the embodied CO2 emissions within inter-provincial trade by using a multiregional input–output approach. The results reveal that the total CO2 emissions of the financial sector in China surged from 4.591 to 12.423 Tg CO2-eq between 2012 and 2020. The regions with the highest annual net CO2 emissions are Anhui (0.244 Tg), Zhejiang (0.242 Tg), and Henan (0.211 Tg). The key factors influencing net CO2 emissions are in the following order of importance: net CO2 density, per capita added value of service industry, the proportion of finances in service industries, and population size. Based on the findings, this study provides policy implications: reducing net carbon intensity, enacting tailored carbon tax policies based on embodied CO2 emissions, and fostering interdepartmental collaboration to address the impact of carbon leakage.

Abstract Background Recent research has demonstrated that the use of artificial intelligence (AI) in radiotherapy (RT) has significantly streamlined the process for physicians to treat patients with tumors; however, bibliometric studies examining the correlation between AI and RT are not available. Providing a thorough overview of the knowledge structure and research hotspots between AI and RT was the main goal of the current study. Method A search was conducted on the Web of Science Core Collection (WoSCC) database for publications pertaining to AI and RT between 2003 and 2023. VOSviewers, CiteSpace, and the R program “bibliometrix” were used to do the bibliometric analysis. Results The analysis comprised 615 publications from 64 countries, with USA and China leading the pack. Since 2017, there have been more and more publications about RT and AI every year. The research center that made the biggest contribution to this topic was Maastricht University. The most articles published journal in this field was Frontiers in Oncology, while Medical Physics received the greatest number of citations. Dekker Andre is the author with the greatest number of published articles, while Philippe Lambin was the most often co-cited author. In the newly identified research hotspots, “autocontouring algorithm”, “deep learning”, and “machine learning” stand out as the main terms. Conclusion In fact, our bibliometric analysis offers insightful information on current research directions and advancements pertaining to the use of AI in RT. For academics looking to understand the connection between AI and RT, this study is a great resource because it highlights current research frontiers and hot trends.

Abstract Background Tea is an important cash crop and buds are its main product. To elucidate the molecular mechanism of the sprouting time of tea plants, ‘Yuchunzao’, which was an early sprouting tea cultivar, was studied. ‘Echa 1’, sprout one week later than ‘Yuchunzao’ in spring, was used as the control. Results A total of 26 hormonal compounds and its derivatives in tea plants were qualified by using Ultra Performance Liquid Chromatography-Tandem mass spectrometry (UPLC-MS/MS). The result showed that GA20, GA3 and ICA were significantly different in ‘Yuchunzao’ than in ‘Echa 1’, with GA20 and GA3 up-regulated and ICA down-regulated. Based on the Illumina platform, transcriptome analysis revealed a total of 5,395 differentially expressed genes (DEGs). A diterpenoid biosynthesis related gene, gibberellin 2-oxidase 1 (CsGA2ox1), was downregulated in ‘Yuchunzao’ compared to ‘Echa 1’. CsGA2ox1 regulate the transformation of GA different forms in plants. The relative expression of CsGA2ox1 showed an adverse trend with the content of GA20 and GA3. Our results suggest that down regulation of CsGA2ox1 resulted in the accumulation of GA3 and GA20, and then promoted sprout of ‘Yuchunzao’. Conclusion This study provides theoretical basis of tea plants sprout and guides the tea breeding in practice.

Abstract For the polarization multiplexing requirements in all-optical networks, this work presents a compact all-fiber polarization beam splitter (PBS) based on dual-core photonic crystal fiber (PCF) and an elliptical gold layer. Numerical analysis using the finite element method (FEM) demonstrates that the mode modulation effect of the central gold layer effectively reduces the dimensions of the proposed PBS. By determining reasonable structural parameters of the proposed PCF, the coupling length ratio (CLR) between X- and Y-polarized super-modes can approach 2, achieving a minimal device length of 0.122 mm. The PBS exhibits a maximum extinction ratio (ER) of − 65 dB at 1.55 μm, with an operating bandwidth spanning 100 nm (1.5–1.6 μm) and a stable insertion loss (IL) of ~ 1.5 dB at 1.55 μm. Furthermore, the manufacture feasibility and performance verification scheme are also investigated. It is widely anticipated that the designed PBS will play a crucial role in the ongoing development process of miniaturization and integration of photonic devices.

Abstract Objectives The aim of this work was to assess dynamic cytokine profiles associated with bloodstream infection (BSI) caused by Klebsiella pneumoniae (Kpn) and investigate the clinical features associated with mortality. Methods A total of 114 patients with positive BSI-Kpn and 12 sepsis individuals without blood positive bacteria culture were followed up. Cytokine profiles were analyzed by multiplex immunoassay on the first, third, seventh and fourteenth day after diagnosis. The test cytokines included arginase, interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-12 (p70), and IL-23. The minimum inhibitory concentration (MIC) of 24 antibiotics were tested for BSI-Kpn. Risk factors associated with the 30-day mortality and 120-day mortality were evaluated using logistic analyses and nomogram. Results There were 55 out of 114 patients with BSI-Kpn were included. All isolates showed high susceptibility rate to novel avibactam combinations. The level of arginase was the highest in carbapenem-resistant Kpn (CRKP) patients. The AUCs of arginase, TNF-α and IL-4 reached 0.726, 0.495, and 0.549, respectively, whereas the AUC for the combination of these three cytokines was 0.805. Notably, 120-day mortality in patients with CRKP was higher than carbapenem-sensitive K. pneumoniae (CSKP). Furthermore, the long-term and high levels of IL-6 and IL-10 were associated with death. Conclusions High expression of arginase is correlated with CRKP. In addition, BSI-CRKP could result in indolent clinic course but poor long-term prognosis. Continuous increase of IL-6 and IL-10 were associated with mortality.

Abstract Tumour metabolic reprogramming is pivotal for tumour survival and proliferation. Investigating potential molecular mechanisms within the heterogeneous and clinically aggressive triple-negative breast cancer (TNBC) subtype is essential to identifying novel therapeutic targets. Accordingly, we investigated the role of branched-chain α-keto acid dehydrogenase kinase (BCKDK) in promoting tumorigenesis in TNBC. We analysed The Cancer Genome Atlas dataset and immunohistochemically stained surgical specimens to investigate BCKDK expression and its prognostic implications in TNBC. The effects of BCKDK on tumorigenesis were assessed using cell viability, colony formation, apoptosis, and cell cycle assays, and subsequently validated in vivo. Metabolomic screening was performed via isotope tracer studies. The downstream target was confirmed using mass spectrometry and a co-immunoprecipitation experiment coupled with immunofluorescence analysis. Upstream transcription factors were also examined using chromatin immunoprecipitation and luciferase assays. BCKDK was upregulated in TNBC tumour tissues and associated with poor prognosis. BCKDK depletion led to reduced cell proliferation both in vitro and vivo. MYC-associated zinc finger protein (MAZ) was confirmed as the major transcription factor directly regulating BCKDK expression in TNBC. Mechanistically, BCKDK interacted with glucose-6-phosphate dehydrogenase (G6PD), leading to increased flux in the pentose phosphate pathway for macromolecule synthesis and detoxification of reactive oxygen species. Forced expression of G6PD rescued the growth defect in BCKDK-deficient cells. Notably, the small-molecule inhibitor of BCKDK, 3,6-dichlorobenzo(b)thiophene-2-carboxylic acid, exhibited anti-tumour effects in a patient-derived tumour xenograft model. Our findings hold significant promise for developing targeted therapies aimed at disrupting the MAZ/BCKDK/G6PD signalling pathway, offering potential advancements in treating TNBC through metabolic reprogramming.

The STK11 gene mutation is a common genetic alteration in non-small cell lung cancer (NSCLC) and is significantly associated with poor responses to current immunotherapy regimens. Despite its prevalence, there is currently no established standard for front-line treatment in this subtype of NSCLC, underscoring the increasing need for personalized therapeutic strategies. In this report, we present a case of a patient with STK11-mutant NSCLC who was treated with first-line cadonilimab (10mg/kg) in combination with pemetrexed (500mg/m^2) plus carboplatin (AUC=5), resulting in a notable extension of progression-free survival (PFS). This case highlights the potential efficacy and feasibility of combining immunotherapy with chemotherapy in patients with STK11-mutant NSCLC. Additionally, we provide a review of recent advancements in research related to STK11 mutations in lung cancer as reported in the literature.

Bisphenol S (BPS) is widely presented and affects aging with unclear mechanisms. Here, we applied C. elegans to evaluate the effects of BPS on lifespan and healthspan and to investigate the underlying mechanisms. Both early-life and whole-life exposure to BPS at environmentally relevant doses (0.6, 6, 60 μg/L) significantly decreased lifespan, and healthspan (body bend, pharyngeal pumping, and lipofuscin accumulation). BPS exposure impaired mitochondrial structure and function, which promoted ROS production to induce oxidative stress. Furthermore, BPS increased expressions of the insulin/IGF-like signaling (IIS). Also, BPS inhibited expression of the IIS transcription factor daf-16 and its downstream anti-oxidative genes. Quercetin effectively improved BPS-induced oxidative stress byreversing BPS-regulated IIS/daf-16 pathway and anti-oxidative gene expressions. In daf-2 and daf-16 mutants, the effects of BPS and quercetin on lifespan, healthspan, oxidative stress, and anti-oxidative genes expressions were reversed, demonstrating the requirement of IIS/daf-16 for aging regulation. Molecular docking and molecular dynamics simulations confirmed the stable interaction between DAF-2 and BPS mainly via three residues (VAL1260, GLU1329, and MET1395), which was attenuated by quercetin. Our results highlighted that adverse effects of BPS on impairing lifespan and healthspan by affecting IIS/daf-16 function against mitochondrial stress, which could be inhibited by quercetin treatment. Thus, we first revealed the underlying mechanisms of BPS-induced aging and the potential treatment.