Rastonia solanacearum type â ¢ effectors target host 14-3-3 proteins to suppress plant immunity.

14-3-3 proteins play important roles in plant metabolism and stress response. Tomato 14-3-3 proteins, SlTFT4 and SlTFT7, serve as hubs of plant immunity and are targeted by some pathogen effectors. Ralstonia solanacearum with more than 70 type Ⅲ effectors (T3Es) is one of the most destructive plant pathogens. However, little is known on whether R. solanacearum T3Es target SlTFT4 and SlTFT7 and hence interfere with plant immunity. We first detected the associations of SlTFT4/SlTFT7 with R. solanacearum T3Es by luciferase complementation assay, and then confirmed the interactions by yeast two-hybrid approach. We demonstrated that 22 Ralstonia T3Es were associated with both SlTFT4 and SlTFT7, and five among them suppressed the hypersensitive response induced by MAPKKKα, a protein kinase which associated with SlTFT4/SlTFT7. We further demonstrated that suppression of MAPKKKα-induced HR and plant basal defense by the T3E RipAC depend on its association with 14-3-3 proteins. Our findings firstly demonstrate that R. solanacearum T3Es can manipulate plant immunity by targeting 14-3-3 proteins, SlTFT4 and SlTFT7, providing new insights into plant-R. solanacearum interactions.

Unveiling community adaptations to extreme heat events using mobile phone location data.

The escalating frequency, duration, and intensity of extreme heat events have posed a significant threat to human society in recent decades. Understanding the dynamic patterns of human mobility under extreme heat will contribute to accurately assessing the risk of extreme heat exposure. This study leverages an emerging geospatial data source, anonymous cell phone location data, to investigate how people in different communities adapt travel behaviors responding to extreme heat events. Taking the Greater Houston Metropolitan Area as an example, we develop two indices, the Mobility Disruption Index (MDI) and the Activity Time Shift Index (ATSI), to quantify diurnal mobility changes and activity time shift patterns at the city and intra-urban scales. The results reveal that human mobility decreases significantly in the daytime of extreme heat events in Houston while the proportion of activity after 8 p.m. is increased, accompanied with a delay in travel time in the evening. Moreover, these mobility-decreasing and activity-delaying effects exhibited substantial spatial heterogeneity across census block groups. Causality analysis using the Geographical Convergent Cross Mapping (GCCM) model combined with correlation analyses indicates that people in areas with a high proportion of minorities and poverty are less able to adopt heat adaptation strategies to avoid the risk of heat exposure. These findings highlight the fact that besides the physical aspect of environmental justice on heat exposure, the inequity lies in the population's capacity and knowledge to adapt to extreme heat. This research is the first of the kind that quantifies multi-level mobility for extreme heat responses, and sheds light on a new facade to plan and implement heat mitigations and adaptation strategies beyond the traditional approaches.

Associations of blood cell indices and anemia with risk of incident dementia: A prospective cohort study of 313,448 participants.

INTRODUCTION: Low hemoglobin and anemia are associated with cognitive impairment and Alzheimer's disease (AD). However, the associations of other blood cell indices with incident dementia risk and the underlined mechanisms are unknown. METHODS: Three hundred thirteen thousand four hundred forty-eight participants from the UK Biobank were included. Cox and restricted cubic spline models were used to investigate linear and non-linear longitudinal associations. Mendelian randomization analysis was used to identify causal associations. Linear regression models were used to explore potential mechanisms driven by brain structures. RESULTS: During a mean follow-up of 9.03 years, 6833 participants developed dementia. Eighteen indices were associated with dementia risk regarding erythrocytes, immature erythrocytes, and leukocytes. Anemia was associated with a 56% higher risk of developing dementia. Hemoglobin and red blood cell distribution width were causally associated with AD. Extensive associations exist between most blood cell indices and brain structures. DISCUSSION: These findings consolidated associations between blood cells and dementia. HIGHLIGHT: Anemia was associated with 56% higher risk for all-cause dementia. Hematocrit percentage, mean corpuscular volume, platelet crit, and mean platelet volume had U-shaped associations with incident dementia risk. Hemoglobin (HGB) and red blood cell distribution width had causal effects on Alzheimer's risk. HGB and anemia were associated with brain structure alterations.

Population Dynamics, Effective Soil Factors, and LAMP Detection Systems for Phytophthora Species Associated with Kiwifruit Diseases in China.

China has the largest area of kiwifruit production in the world. Pathogens associated with root diseases of kiwi trees have not been investigated extensively. In this research, three Phytophthora species, Phytophthora cactorum, Phytophthora cinnamomi, and Phytophthora lateralis, which are pathogenic to kiwi trees in the main planting areas of China, were studied. The population densities of these species in 128 soil samples from 32 kiwi orchards in 2017 and 2018 were measured using multiplex real-time quantitative PCR based on the ras-related protein gene Ypt1. P. cactorum was the most widely distributed of the three species in orchards of the Zhouzhi and Meixian prefectures. We used redundancy analysis to examine soil factors in the kiwi orchards to understand their effects on the population densities of the Phytophthora species. The redundancy analysis indicated that soil temperature and pH were significantly correlated with the abundance of P. cactorum and P. cinnamomi. In addition, two loop-mediated isothermal amplification detection systems for P. cactorum were developed based on the tigA gene. The color-change detection system proved to be accurate, sensitive, and faster than quantitative PCR. The results of this study, along with the loop-mediated isothermal amplification detection systems, will be of great use in the control of Phytophthora diseases for the production of kiwifruits in China.

MiR-33a-5p targets NOMO1 to modulate human cardiomyocyte progenitor cells proliferation and differentiation and apoptosis.

PURPOSE: MicroRNA (miRNA) is known to be involved in the pathological process of congenital heart disease (CHD), and nodal modulator1 (NOMO1) is a critical determinant of heart formation. The present study aims to discover the effect of miR-33a-5p and NOMO1 on CHD. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect expressions of miR-33a-5p mimic or inhibitor and overexpressed NOMO1 plasmid orNOMO1 knockdown. Human cardiomyocyte progenitor cells (hCMPCs) proliferation was measured by cell counting kit-8 (CCK-8) at 24, 48 and 72 h. Flow cytometry was applied to investigate hCMPCs cell cycle progression and apoptosis. Expressions of cell apoptotic proteins Bax, Cleaved(C) caspase-3 and Bcl-2, and expressions of cardiomyocyte differentiation markers GATA4, troponin T (cTnT) and myocyte enhancer factor2C (MEF2C) in hCMPCs were identified by qRT-PCR and western blot. Target genes and potential binding sites of NOMO1 and miR-33a-5p were predicted with Targetscan 7.2, and was confirmed through dual-luciferase reporter assay. RESULTS: Up-regulation of miR-33a-5p inhibited hCMPCs proliferation, cell cycle G0/S transition but promoted hCMPCs apoptosis, which was partially mitigated by overexpressed NOMO1. NOMO1 was the target gene of miR-33a-5p. Expressions of Bax and C caspase-3 were enhanced but expressions of Bcl-2, GATA4, cTnT and MEF2C were reduced by up-regulation of miR-33a-5p, which was partially mitigated by overexpressed NOMO1. CONCLUSION: Up-regulation of miR-33a-5p inhibited hCMPCs proliferation, cell cycle G0/S transition and differentiation into cardiomyocytes but promoted apoptosis via targeting NOMO1.

Disparities of population exposed to flood hazards in the United States.

This study integrates publicly available datasets to provide a county-based assessment of socio-economic disparities of population exposure to flood hazards in the United States. Statistical analyses were applied to reveal the national trends and local deviations from the trends. Results show that approximately 21.8 million (6.87% of) U.S. population are exposed to 100-year-flood in 2015, and most of the exposure is near water bodies (e.g. ocean and rivers). Additionally, communities near water bodies are more responsive to potential flood hazards by avoiding residence in flood zones than inland communities. At the national scale, economically disadvantaged population are more likely to reside in flood zones than outside. At the local scale, economically disadvantaged population tend to reside in flood zones in inland areas, while coastal flood zones are more occupied by wealthier and elderly people. These findings point to an alarming situation of inland communities where people are generally less responsive to flood hazards and people in flood zones are in a lower economic condition. Using "hot spot" analysis, local clusters of disadvantaged population groups with high flood exposure were identified. Overall, this study provides important baseline information for policymaking at different levels of administration and pinpoints local areas where diversified and ad hoc strategies are needed to mitigate flood risk in communities with diverse socio-economic conditions. This study provides empirical evidence of socio-economic disparities and environmental injustice associated with flood exposure in the U.S. and offers valuable insights to the underlying factors.

De Novo Assembly and Analysis of Polygonatum sibiricum Transcriptome and Identification of Genes Involved in Polysaccharide Biosynthesis.

Polygonatum sibiricum polysaccharides (PSPs) are used to improve immunity, alleviate dryness, promote the secretion of fluids, and quench thirst. However, the PSP biosynthetic pathway is largely unknown. Understanding the genetic background will help delineate that pathway at the molecular level so that researchers can develop better conservation strategies. After comparing the PSP contents among several different P. sibiricum germplasms, we selected two groups with the largest contrasts in contents and subjected them to HiSeq2500 transcriptome sequencing to identify the candidate genes involved in PSP biosynthesis. In all, 20 kinds of enzyme-encoding genes were related to PSP biosynthesis. The polysaccharide content was positively correlated with the expression patterns of ß-fructofuranosidase (sacA), fructokinase (scrK), UDP-glucose 4-epimerase (GALE), Mannose-1-phosphate guanylyltransferase (GMPP), and UDP-glucose 6-dehydrogenase (UGDH), but negatively correlated with the expression of Hexokinase (HK). Through qRT-PCR validation and comprehensive analysis, we determined that sacA, HK, and GMPP are key genes for enzymes within the PSP metabolic pathway in P. sibiricum. Our results provide a public transcriptome dataset for this species and an outline of pathways for the production of polysaccharides in medicinal plants. They also present more information about the PSP biosynthesis pathway at the molecular level in P. sibiricum and lay the foundation for subsequent research of gene functions.

Transplantation of Human Neural Stem Cells in a Parkinsonian Model Exerts Neuroprotection via Regulation of the Host Microenvironment.

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons and consequent dopamine (DA) deficit, and current treatment still remains a challenge. Although neural stem cells (NSCs) have been evaluated as appealing graft sources, mechanisms underlying the beneficial phenomena are not well understood. Here, we investigate whether human NSCs (hNSCs) transplantation could provide neuroprotection against DA depletion by recruiting endogenous cells to establish a favorable niche. Adult mice subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were transplanted with hNSCs or vehicle into the striatum. Behavioral and histological analyses demonstrated significant neurorescue response observed in hNSCs-treated animals compared with the control mice. In transplanted animals, grafted cells survived, proliferated, and migrated within the astrocytic scaffold. Notably, more local astrocytes underwent de-differentiation, acquiring the properties of NSCs or neural precursor cells (NPCs) in mice given hNSCs. Additionally, we also detected significantly higher expression of host-derived growth factors in hNSCs-transplanted mice compared with the control animals, together with inhibition of local microglia and proinflammatory cytokines. Overall, our results indicate that hNSCs transplantation exerts neuroprotection in MPTP-insulted mice via regulating the host niche. Harnessing synergistic interaction between the grafts and host cells may help optimize cell-based therapies for PD.

DNA electrochemical sensor for detection of PRSS1 point mutation based on restriction endonuclease technique.

To construct a restriction endonuclease based biosensor technology for PRSS1 genotyping. We designed a thiol-modified hairpin probe where the neck has EcoRI endonuclease recognition sites according to the PRSS1 gene c.410 C>T (p.T137 M) mutation and it was fixed on the gold electrode. Different charge generated by the binding of MB to phosphate groups of DNA before and after hybridization was used for distinguishing the different genotypes and quantity. This showed that the novel sensor can better distinguish the complementary sequence, single-base mismatches, and completely noncomplementary sequences, and the linear range for the logarithm was Y=-0.0242 X+0.1574, R=0.9912(Y=current, X=log target DNA concentration); the detection limit for DNA detection is estimated to be 50 fM.

Modeling land use and land cover changes in a vulnerable coastal region using artificial neural networks and cellular automata.

As one of the most vulnerable coasts in the continental USA, the Lower Mississippi River Basin (LMRB) region has endured numerous hazards over the past decades. The sustainability of this region has drawn great attention from the international, national, and local communities, wanting to understand how the region as a system develops under intense interplay between the natural and human factors. A major problem in this deltaic region is significant land loss over the years due to a combination of natural and human factors. The main scientific and management questions are what factors contribute to the land use land cover (LULC) changes in this region, can we model the changes, and how would the LULC look like in the future given the current factors? This study analyzed the LULC changes of the region between 1996 and 2006 by utilizing an artificial neural network (ANN) to derive the LULC change rules from 15 human and natural variables. The rules were then used to simulate future scenarios in a cellular automation model. A stochastic element was added in the model to represent factors that were not included in the current model. The analysis was conducted for two sub-regions in the study area for comparison. The results show that the derived ANN models could simulate the LULC changes with a high degree of accuracy (above 92 % on average). A total loss of 263 km(2) in wetlands from 2006 to 2016 was projected, whereas the trend of forest loss will cease. These scenarios provide useful information to decision makers for better planning and management of the region.

Serum trypsin and TCR as novel markers for predicting disease activity in IgG4-related disease.

BACKGROUND: IgG4-related disease (IgG4-RD) is a novel disease named in recent years. Because of its varied clinical manifestations, like tumor but not tumor, it brings a great challenge to clinical diagnosis. Trypsin and T-cell receptor (TCR) are thought to mediate the regulation of B cell maturation, survival and antibody production. In this study, we investigated the clinical features and important novel markers of IgG4-RD. MATERIAL AND METHODS: A prospective cohort study of 22 patients with IgG4-RD was carried out from May 2009 to December 2012, and 65 cases with acute pancreatitis, 60 cases with pancreatic cancer and 120 healthy individuals were studied as controls. Serum TCR, trypsin and IgG4 levels were measured during pre- and post-treatment in the patients with IgG4-RD and their correlations with IgG4 were also assessed. RESULTS: Serum IgG4 and IgE levels in all patients were significantly increased, and tumor markers (carbohydrate antigen 19-9 and/or carbohydrate antigen 125) were also increased (12/22). Serum trypsin in patients with IgG4-RD was lower than in the ones with acute pancreatitis, pancreatic cancer, and healthy individuals. But serum TCR of IgG4-RD was significantly higher than in the pancreatic cancer group and normal controls and it was inversely correlated with the levels of IgG4 (r = -3.160, p = 0.042). CONCLUSIONS: The results indicate that serum TCR and trypsin might be useful markers for predicting disease activity in IgG4-RD.

Magnetic Composite Photocatalyst NiFe2O4/ZnIn2S4/Biochar for Efficient Removal of Antibiotics in Water Under Visible Light: Performance, Mechanism and Pathway.

The widespread presence of antibiotics in aquatic environments, resulting from excessive use and accumulation, has raised significant concerns. A NiFe2O4/ZnIn2S4/ Biochar (NFO/ZIS/BC) magnetic nanocomposite was successfully synthesized, demonstrating significantly enhanced electron-hole separation properties. Comprehensive investigations were conducted to evaluate the impact of various parameters, including catalyst mass, pH, and the presence of co-existing ions on the composite's performance. The nanoparticles of NiFe2O4 (NFO) and ZnIn2S4 (ZIS) were found to improve the surface stability and sulfamethoxazole removal capabilities of porous biochar, while also demonstrating high total organic carbon removal efficiencies. •O2⁻ and h⁺ were identified as the predominant reactive oxygen species (ROS) in NFO/ZIS/BC-4 during the degradation process. The degradation outcomes of sulfamethoxazole under natural sunlight and water conditions were consistent with laboratory findings, affirming the robust applicative potential of NFO/ZIS/BC. Density functional theory (DFT) calculations were performed to elucidate the photocatalytic mechanism and identify potential intermediate products. Additionally, the types of heterojunctions present in the system were characterized and discussed. After multiple iterations, NFO/ZIS/BC-4 maintained effective photodegradation capabilities through five cycles. This study presents an effective method for the treatment of antibiotics in aquatic environments, offering significant potential for environmental applications.

Cracking modes and force dynamics in the insertion of neural probes into hydrogel brain phantom.

Objective. The insertion of penetrating neural probes into the brain is crucial for advancing neuroscience, yet it involves various inherent risks. Prototype probes are typically inserted into hydrogel-based brain phantoms and the mechanical responses are analyzed in order to inform the insertion mechanics duringin vivoimplantation. However, the underlying mechanism of the insertion dynamics of neural probes in hydrogel brain phantoms, particularly the phenomenon of cracking, remains insufficiently understood. This knowledge gap leads to misinterpretations and discrepancies when comparing results obtained from phantom studies to those observed under thein vivoconditions. This study aims to elucidate the impact of probe sharpness and dimensions on the cracking mechanisms and insertion dynamics characterized during the insertion of probes in hydrogel phantoms.Approach. The insertion of dummy probes with different shank shapes defined by the tip angle, width, and thickness is systematically studied. The insertion-induced cracks in the transparent hydrogel were accentuated by an immiscible dye, tracked byin situimaging, and the corresponding insertion force was recorded. Three-dimensional finite element analysis models were developed to obtain the contact stress between the probe tip and the phantom.Main results. The findings reveal a dual pattern: for sharp, slender probes, the insertion forces remain consistently low during the insertion process, owing to continuously propagating straight cracks that align with the insertion direction. In contrast, blunt, thick probes induce large forces that increase rapidly with escalating insertion depth, mainly due to the formation of branched crack with a conical cracking surface, and the subsequent internal compression. This interpretation challenges the traditional understanding that neglects the difference in the cracking modes and regards increased frictional force as the sole factor contributing to higher insertion forces. The critical probe sharpness factors separating straight and branched cracking is identified experimentally, and a preliminary explanation of the transition between the two cracking modes is derived from three-dimensional finite element analysis.Significance. This study presents, for the first time, the mechanism underlying two distinct cracking modes during the insertion of neural probes into hydrogel brain phantoms. The correlations between the cracking modes and the insertion force dynamics, as well as the effects of the probe sharpness were established, offering insights into the design of neural probes via phantom studies and informing future investigations into cracking phenomena in brain tissue during probe implantations.

Array-wide uniform PEDOT:PSS electroplating from potentiostatic deposition.

Electroplating of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) is important in many neuroelectronic applications but is challenging to achieve uniformity on large-scale microelectrode arrays (MEA) using conventional galvanostatic methods. In this study, we address this challenge through a potentiostatic method and demonstrate highly uniform electroplating of PEDOT:PSS on MEA with more than one hundred electrodes, all at cellular sizes. The validation of this approach involves comparisons with galvanostatic deposition methods, showcasing unparalleled deposition yield and uniformity. Systematic electrochemical characterizations reveal similarities in structure and stability from potentiostatic deposited coatings. The advances developed here establish the potentiostatic method and detailed process to achieve a uniform coating of PEDOT:PSS on large-scale MEA, with broad utility in neuroelectronics.

Multifunctional Nanomesh Enables Cellular-Resolution, Elastic Neuroelectronics.

Silicone-based devices have the potential to achieve an ideal interface with nervous tissue but suffer from scalability, primarily due to the mechanical mismatch between established electronic materials and soft elastomer substrates. This study presents a novel approach using conventional electrode materials through multifunctional nanomesh to achieve reliable elastic microelectrodes directly on polydimethylsiloxane (PDMS) silicone with an unprecedented cellular resolution. This engineered nanomesh features an in-plane nanoscale mesh pattern, physically embodied by a stack of three thin-film materials by design, namely Parylene-C for mechanical buffering, gold (Au) for electrical conduction, and Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) for improved electrochemical interfacing. Nanomesh elastic neuroelectronics are validated using single-unit recording from the small and curvilinear epidural surface of mouse dorsal root ganglia (DRG) with device self-conformed and superior recording quality compared to plastic control devices requiring manual pressing is demonstrated. Electrode scaling studies from in vivo epidural recording further revealed the need for cellular resolution for high-fidelity recording of single-unit activities and compound action potentials. In addition to creating a minimally invasive device to effectively interface with DRG sensory afferents at a single-cell resolution, this study establishes nanomeshing as a practical pathway to leverage traditional electrode materials for a new class of elastic neuroelectronics.

Plasma metabolic profiles predict future dementia and dementia subtypes: a prospective analysis of 274,160 participants.

BACKGROUND: Blood-based biomarkers for dementia are gaining attention due to their non-invasive nature and feasibility in regular healthcare settings. Here, we explored the associations between 249 metabolites with all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VaD) and assessed their predictive potential. METHODS: This study included 274,160 participants from the UK Biobank. Cox proportional hazard models were employed to investigate longitudinal associations between metabolites and dementia. The importance of these metabolites was quantified using machine learning algorithms, and a metabolic risk score (MetRS) was subsequently developed for each dementia type. We further investigated how MetRS stratified the risk of dementia onset and assessed its predictive performance, both alone and in combination with demographic and cognitive predictors. RESULTS: During a median follow-up of 14.01 years, 5274 participants developed dementia. Of the 249 metabolites examined, 143 were significantly associated with incident ACD, 130 with AD, and 140 with VaD. Among metabolites significantly associated with dementia, lipoprotein lipid concentrations, linoleic acid, sphingomyelin, glucose, and branched-chain amino acids ranked top in importance. Individuals within the top tertile of MetRS faced a significantly greater risk of developing dementia than those in the lowest tertile. When MetRS was combined with demographic and cognitive predictors, the model yielded the area under the receiver operating characteristic curve (AUC) values of 0.857 for ACD, 0.861 for AD, and 0.873 for VaD. CONCLUSIONS: We conducted the largest metabolome investigation of dementia to date, for the first time revealed the metabolite importance ranking, and highlighted the contribution of plasma metabolites for dementia prediction.

CLE peptides in vascular development.

The plant vascular system consists of two conductive tissues, phloem and xylem. The vascular meristem, namely the (pro-)cambium, is a stem-cell tissue that gives rise to both xylem and phloem. Recent studies have revealed that CLAVATA3/Embryo Surrounding Region-related (CLE) peptides function in establishing the vascular system through interaction with phytohormones. In particular, TDIF/CLE41/CLE44, phloem-derived CLE peptides, promote the proliferation of vascular cambium cells and prevent them from differentiating into xylem by regulating WOX4 expression through the TDR/PXY receptor. In this review article, we outline recent advances on how CLE peptides function in vascular development in concert with phytohormones through mediating cell-cell communication. The perspective of CLE peptide signaling in vascular development is also discussed.

The impact of concurrent bacterial lung infection on immunotherapy in patients with non-small cell lung cancer: a retrospective cohort study.

Objective: To find out how bacterial lung infections (BLI) affect the effectiveness of therapy and the rate of pneumonia caused by pneumonia related to checkpoint inhibitors (CIP) in patients with non-small cell lung cancer (NSCLC) who are getting immunotherapy with checkpoint inhibitors (ICIs). Patients and methods: 507 NSCLC patients who received at least two ICI treatments between June 2020 and December 2022 at the Affiliated Hospital of Kunming University of Science and Technology(AHKUST) were included in a retrospective cohort study. Based on whether there was a concurrent BLI diagnosis from high-resolution CT scans of the chest, the patients were divided into two groups: 238 in the NSCLC with BLI group (NSCLC-BLI group), and 269 in the NSCLC alone group. The collected therapeutic outcome measures included the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the incidence rate of CIP. We analyzed the effect of BLI on the therapeutic efficacy of ICI treatment and the incidence rate of CIP in NSCLC patients.Inclusion criteria based on NSCLC patients staged I to IV according to the 8th edition of the International Association for Lung Cancer Research (IASLC). Results: The NSCLC-BLI group showed superior ORR to the NSCLC group when treated with ICIs. Multifactorial logistic regression and Cox analyses, adjusted for confounders, identified BLI as an independent positive prognostic factor for ORR (HR=0.482, 95%CI: 0.391-0.550; P<0.001) and PFS (HR=0.619; 95%CI: 0.551-0.771; P<0.001). No correlation between BLI and OS was found. Out of 26 cases of CIP, 12 were in the NSCLC-BLI group and 14 in the NSCLC group, with no significant difference in incidence (P=0.145). Conclusion: NSCLC patients with BLI receiving ICI treatment show superior ORR and PFS compared to NSCLC alone without an increased CIP risk, positioning BLI as a predictive factor for improved outcomes in NSCLC patients receiving ICIs. However, the study has limitations including its retrospective nature and lacking data on BLI bacteria types and levels, which could influence therapy outcomes.