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Abstract Background Patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 2 probably cannot tolerate chemotherapy or other antitumor therapies. Some studies have reported that immunotherapy combined with antiangiogenic therapy is well‐tolerated and shows good antitumor activity. However, the efficacy of this combination as a later‐line therapy in patients with ECOG PS 2 is unclear. This study evaluated the effectiveness and safety of this combination strategy as third‐ or further‐line therapy in stage IV non‐small cell lung cancer (NSCLC) patients with ECOG PS 2. Methods In this retrospective study, patients treated with camrelizumab plus antiangiogenic therapy (bevacizumab, anlotinib, or recombinant human endostatin) were included. Objective response rate (ORR), disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), quality of life (QOL) assessed by ECOG PS, and safety were analyzed. Results Between January 10, 2019, and February 28, 2024, a total of 59 patients were included. The ORR was 35.6% (21/59) and the DCR was 86.4%. With a median follow‐up of 10.5 months (range: 0.7–23.7), the median PFS was 5.5 months (95% confidence interval [CI]: 3.8–7.3) and the median OS was 10.5 months (95% CI: 11.2–13.6). QOL was improved (≥1 reduction in ECOG PS) in 39 patients (66.1%). The most common Grade 3–4 treatment‐related adverse events were hepatic dysfunction (6 [10%]), hypertension (5 [8%]), and hypothyroidism (3 [5%]). There were no treatment‐related deaths. Conclusions Third‐ or further‐line immunotherapy combined with antiangiogenic therapy is well‐tolerated and shows good antitumor activity in stage IV NSCLC patients with ECOG PS 2. Future large‐scale prospective studies are required to confirm the clinical benefits of this combination therapy.

On the premise of clarifying the related concepts of marine industry digitalization, the index system of marine industry digital level is constructed based on the "diamond model" and the projection tracing model is used to measure the digital level of marine industry in 11 coastal provinces and cities from 2014 to 2020; on this basis, the evolution law of the digital level of China marine industry is analyzed in depth. The research found that: the digital level of China's marine industry generally shows a rapid growth trend, however, there are some differences between the coastal provinces in different regions; Regional differences are the dominant factor for the regional differences in the digital level of China's marine industry during the research period. Among them, the northern coastal areas, the eastern coastal region has minimal internal variation, the internal differences in the southern coastal areas are in the middle; The digital agglomeration forms of marine industries in the three marine economic circles have their own characteristics: the coastal provinces and cities in the northern marine economic circle form "high-low" agglomeration type, the coastal provinces and cities in the southern marine economic circle form "low-high" agglomeration type, and the coastal provinces and cities in the eastern marine economic circle form "high-high" agglomeration type.

Objective: A method for the determination of aminophylline residues in edible tissues （muscle, liver and kidney） of pigs by solid-phase extraction combined with high performance liquid chromatography-tandem mass spectrometry was established. Methods: After extracted by methanol, the aminophylline was purified by PRiME HLB solid phase extraction column in one step, and then separated by a C18 chromatographic column. 0.1% formic acid solution and acetonitrile were invoked as the aqueous phase and the organic phase for gradient elution, respectively. Electrospray positive voltage ionization and multi reaction monitoring （MRM） mode are used for compound detection, and matrix matching standard was used for quantification. Results: The analysis of aminophylline drugs was completed within 3.5 minutes, and the results showed good linear relationship （R＞0.998 0） on different matrices in the concentration range of 0.05~1.0 μg/mL. The average recoveries ranged from 87.2% to 101.3%, and the relative standard deviations ranged from 0.7% to 6.2% （n=6）. The detection limit was 2 μg/kg and the quantification limit was 5 μg/kg. Conclusion: The method which is simple and efficient, has good repeatability and high sensitivity. It is suitable for qualitative and quantitative analysis of aminophylline drug residues in edible tissues of pigs.

Abstract Bacteria possess elaborate systems to manage reactive oxygen and nitrogen species (ROS) arising from exposure to the mammalian immune system and environmental stresses. Here we report the discovery of an ROS-sensing RNA-modifying enzyme that regulates translation of stress-response proteins in the gut commensal and opportunistic pathogen Enterococcus faecalis. We analyze the tRNA epitranscriptome of E. faecalis in response to reactive oxygen species (ROS) or sublethal doses of ROS-inducing antibiotics and identify large decreases in N2-methyladenosine (m2A) in both 23 S ribosomal RNA and transfer RNA. This we determine to be due to ROS-mediated inactivation of the Fe-S cluster-containing methyltransferase, RlmN. Genetic knockout of RlmN gives rise to a proteome that mimics the oxidative stress response, with an increase in levels of superoxide dismutase and decrease in virulence proteins. While tRNA modifications were established to be dynamic for fine-tuning translation, here we report the discovery of a dynamically regulated, environmentally responsive rRNA modification. These studies lead to a model in which RlmN serves as a redox-sensitive molecular switch, directly relaying oxidative stress to modulating translation through the rRNA and the tRNA epitranscriptome, adding a different paradigm in which RNA modifications can directly regulate the proteome.

Abstract Four conjugated polymers are integrated with a bacteriorhodopsin D94N‐HmBRI in organic field‐effect transistors (OFETs) with the device architecture of doped Si bottom gate/SiO2 bottom electric/semiconducting polymer/Au electrodes/D94N‐HmBRI top dielectric. Photosensitivity of D94N‐HmBRI in the devices is validated. It is proposed that light activates the conformational change of all‐trans retinal to 13‐cis retinal in D94N‐HmBRI. The D94N‐HmBRI layer then applies momentary dipoles to the semiconductors, affecting threshold voltage, resulting in photosensitivity. Film‐thickness variation, capacitance determination, and grazing‐incidence X‐ray scattering are performed to support the proposed working principle. Quasi dual‐gate OFETs with a highly doped silicon wafer as the bottom gate and light as the top gate are thus realized by combining conjugated polymers with D94N‐HmBRI.

Bacterial pathogens require a variety of micronutrients for growth, including trace metals such as iron, manganese, and zinc (Zn). Despite their relative abundance in host environments, access to these metals is severely restricted during infection due to host-mediated defense mechanisms collectively known as nutritional immunity. Despite a growing appreciation of the importance of Zn in host-pathogen interactions, the mechanisms of Zn homeostasis and the significance of Zn to the pathophysiology of E. faecalis, a major pathogen of nosocomial and community-associated infections, have not been thoroughly investigated. Here, we show that E. faecalis encoded ABC-type transporter AdcACB and an orphan substrate-binding lipoprotein AdcAII that work cooperatively to maintain Zn homeostasis. Simultaneous inactivation of adcA and adcAII or the entire adcACB operon led to a significant reduction in intracellular Zn under Zn-restricted conditions and heightened sensitivity to Zn-chelating agents including human calprotectin, aberrant cell morphology, and impaired fitness in serum ex vivo. Additionally, inactivation of adcACB and adcAII significantly reduced bacterial tolerance toward cell envelope-targeting antibiotics. Finally, we showed that the AdcACB/AdcAII system contributes to E. faecalis virulence in a Galleria mellonella invertebrate infection model and in two catheter-associated mouse infection models that recapitulate many of the host conditions associated with enterococcal human infections. Collectively, this report reveals that high-affinity Zn import is important for the pathogenesis of E. faecalis establishing the surface-associated AdcA and AdcAII lipoproteins as potential therapeutic targets.

We have previously demonstrated the potential of gelatin films as a memory device, offering a novel approach for writing, reading, and erasing through the manipulation of gelatin structure and bound water content. Here, we discovered that incorporating a bacteriorhodopsin (BR)–lipid membrane into the gelatin devices can further increase the electron conductivity of the polypeptide-bound water network and the ON/OFF ratio of the device by two folds. Our photocurrent measurements show that the BR incorporated in the membrane sandwiched in a gelatin device can generate a net proton flow from the counter side to the deposited side of the membrane. This leads to the establishment of non-electroneutrality on the gelatin films adjacent to the BR-incorporated membrane. Our Raman spectroscopy results show that BR proton pumping in the ON state gelatin device increases the bound water presence and promotes polypeptide unwinding compared to devices without BR. These findings suggest that the non-electroneutrality induced by BR proton pumping can increase the extent of polypeptide unwinding within the gelatin matrix, consequently trapping more bound water within the gelatin-bound water network. The resulting rise in hydrogen bonds could expand electron transfer routes, thereby enhancing the electron conductivity of the memory device in the ON state.

Background: Plant microbiota contributes to plant growth and health, including enhancing plant resistance to various diseases. Despite remarkable progress in understanding diseases resistance in plants, the precise role of rhizosphere microbiota in enhancing watermelon resistance against soil-borne diseases remains unclear. Here, we constructed a synthetic community (SynCom) of 16 core bacterial strains obtained from the rhizosphere of grafted watermelon plants. We further simplified SynCom and investigated the role of bacteria with synergistic interactions in promoting plant growth through a simple synthetic community. Results: Our results demonstrated that the SynCom significantly enhanced the growth and disease resistance of ungrafted watermelon grown in non-sterile soil. Furthermore, analysis of the amplicon and metagenome data revealed the pivotal role of Pseudomonas in enhancing plant health, as evidenced by a significant increase in the relative abundance and biofilm-forming pathways of Pseudomonas post-SynCom inoculation. Based on in vitro co-culture experiments and bacterial metabolomic analysis, we selected Pseudomonas along with seven other members of the SynCom that exhibited synergistic effects with Pseudomonas. It enabled us to further refine the initially constructed SynCom into a simplified SynCom comprising the eight selected bacterial species. Notably, the plant-promoting effects of simplified SynCom were similar to those of the initial SynCom. Furthermore, the simplified SynCom protected plants through synergistic effects of bacteria. Conclusions: Our findings suggest that the SynCom proliferate in the rhizosphere and mitigate soil-borne diseases through microbial synergistic interactions, highlighting the potential of synergistic effects between microorganisms in enhancing plant health. This study provides a novel insight into using the functional SynCom as a promising solution for sustainable agriculture. 6UoEKpA3MAKccxe2Gy9v1z Video Abstract [ABSTRACT FROM AUTHOR]