Neutrophil PPIF exacerbates lung ischemia-reperfusion injury after lung transplantation by promoting calcium overload-induced neutrophil extracellular traps formation.

Lung ischemia-reperfusion (I/R) injury is the main risk factor for primary graft dysfunction and patient death after lung transplantation (LTx). It is widely accepted that the main pathological mechanism of lung I/R injury are calcium overload, oxygen free radical explosion and neutrophil-mediated damage, which leading to the lack of effective treatment options. The aim of this study was to further explore the mechanisms of lung I/R injury after LTx and to provide potential therapeutic strategies. Our bioinformatics analysis revealed that the neutrophil extracellular traps (NETs) formation was closely involved in lung I/R injury after LTx, which was accompanied by up-regulation of peptidylprolyl isomerase F (PPIF) and peptidyl arginine deiminase 4 (PADI4). We further established an orthotopic LTx mouse model to simulate lung I/R injury in vivo, and found that PPIF and PADI4 inhibitors effectively reduced neutrophil infiltration, NETs formation, inflammatory response, and lung I/R injury. In the neutrophil model induced by HL-60 cell line in vitro, we found that PPIF inhibitor cyclosporin A (Cys A) better alleviated calcium overload induced inflammatory response, reactive oxygen species content and NETs formation. Further study demonstrated that interfering with neutrophil PPIF protected mitochondrial function by alleviating store-operated calcium entry (SOCE) during calcium overload and played the above positive role. On this basis, we found that the reduction of calcium content in neutrophils was accompanied by the inhibition of calcineurin (CN) and nuclear factor of activated T cells (NFAT). In conclusion, our findings suggested that neutrophil PPIF could serve as a novel biomarker and potential therapeutic target of lung I/R injury after LTx, which provided new clues for its treatment by inhibiting calcium overload-induced NETs formation.

The Small Auxin-Up RNA 50 (SAUR50) Gene from Ammopiptanthus nanus Negatively Regulates Drought Tolerance.

Drought stress is a primary abiotic stress that causes significant losses to forestry and agricultural production. Therefore, exploring drought-responsive genes and their regulatory mechanism is crucial for plant molecular breeding for forestry and agriculture production safety. Small auxin-up RNA (SAUR) proteins are essential in plant growth and development but show functional diversity in stress response. In this study, the transcriptome sequencing data of Ammopiptanthus nanus seedlings revealed that the expression of AnSAUR50 was continuously downregulated under drought stress. Hence, the AnSAUR50 gene was cloned and functionally analyzed in drought response. The results showed that the coding sequence of AnSAUR50 was 315 bp in length and encoded 104 amino acids. The AnSAUR50 protein showed high conservation, possessed a SAUR-specific domain, and localized in the nucleus and cell membrane. The heterologous expression of the AnSAUR50 gene enhanced the drought sensitivity of the transgenic Arabidopsis with a lower survival rate, biomass, and higher malondialdehyde content and relative electrolyte leakage. Moreover, transgenic plants showed shorter root lengths and bigger stomatal apertures, resulting in facilitating water loss under drought stress. The study indicates that AnSAUR50 negatively regulates drought tolerance by inhibiting root growth and stomatal closure, which provides insights into the underlying function and regulatory mechanism of SAURs in plant stress response.

Foliar spraying of boron prolongs preservation period of strawberry fruits by altering boron form and boron distribution in cell.

Boron (B), an essential micronutrient for fruit development, also plays a crucial role in maintaining the shelf life of strawberries (Fragaria ananassa Duch.) by affecting cell wall structure and components. We investigated the distribution pattern of B within cells and cell walls in strawberry fruits under different B levels and revealed the relationship between the B distribution in cell walls and fruit firmness after harvesting. Foliar spraying of 0.1% H3BO3 promoted the growth of strawberry seedlings and improved fruit yield and flesh firmness by 45.7% and 25.6%. During the fruit softening and decay process, the content of bound B and cell wall-B decreased while more B was allocated to the protoplast and apoplast. The changes in B distribution in cells were attributed to cell damage during fruit decay, and B extended the freshness period of the fruits by alleviating the decrease of B distribution in cell walls. After leaving the fruits at room temperature for 10 h, the B content in different cell wall components significantly decreased, while foliar spraying of B alleviated the reduction of B content in covalently bound pectin (CBP), cellulose, and hemicellulose. Meanwhile, B spraying on fruit decreased the activity of cell wall degradation enzymes, including polygalacturonase (PG) and pectin lyase (PL), by 20.2% and 38.1%, while enhancing the demethylation of pectin by increasing pectin methylesterase (PME) activity from 21.6 U/g to 25.7 U/g. Thus, foliar spraying of 0.1% H3BO3 enhances the cross-linking of B with cell wall components and maintains cell wall structure, thereby prolonging the shelf life of strawberry fruits.

Human-robot interaction in motor imagery: A system based on the STFCN for unilateral upper limb rehabilitation assistance.

BACKGROUND: Rehabilitation training based on the brain-computer interface of motor imagery (MI-BCI) can help restore the connection between the brain and movement. However, the performance of most popular MI-BCI system is coarse-level, which means that they are good at guiding the rehabilitation exercises of different parts of the body, but not for the individual component. NEW METHODS: In this paper, we designed a fine-level MI-BCI system for unilateral upper limb rehabilitation assistance. Besides, due to the low discrimination of different sample classes in a single part, a classification algorithm called spatial-temporal filtering convolutional network (STFCN) was proposed that used spatial filtering and deep learning. COMPARISON WITH EXISTING METHODS: Our STFCN outperforms popular methods in recent years using BCI IV 2a and 2b data sets. RESULTS: To verify the effectiveness of our system, we recruited 6 volunteers and collected their data for a four-classification online experiments, resulting in an average accuracy of 62.7 %. CONCLUSION: This fine-level MI-BCI system has good appli-cation prospects, and inspires more exploration of rehabilitation in a single part of the human body.

T cell-related circRNA pairs to predict prognosis of patients with esophageal squamous cell carcinoma.

The prognosis for esophageal squamous cell carcinoma (ESCC), a prevalent and aggressive form of cancer, remains poor despite advancements in treatment options. Addressing the gap in comprehensive prognostic information derived from circRNA expression profiles for ESCC, our study aimed to establish a linkage between circRNA expressions and ESCC prognosis. To achieve this, we first developed an optimized prognostic model named T cell-related risk score (TRRS), which integrates T cell-associated features with machine learning algorithms. In parallel, we re-analyzed existing RNA-seq datasets to redefine the expression profiles of circRNAs and mRNAs. Utilizing the TRRS as a foundational "bridge," we identified circRNAs correlated with TRRS, leading to the development of a novel circRNA pair-based prognostic model, the TCRS, which is independent of specific expression levels. Further investigations uncovered two circRNAs, circNLK(5,6,7).1 and circRC3H1(2).1, with potential functional significance. These findings underscore the utility of these risk scores as tools for predicting overall survival and identifying potential therapeutic targets for ESCC patients.

Correlation between lipid levels at different stages of pregnancy and pregnancy outcome and complications.

OBJECTIVE: To explore correlation between lipid levels at different stages of pregnancy and outcomes and complications of pregnancy. METHODS: The clinical data of 1000 parturients were retrospectively analyzed. The incidence of perinatal complications was counted, and the blood lipid levels of pregnant women with and without complications during pregnancy were compared. Additionally, the pregnancy outcomes of women with different lipid levels were compared. RESULTS: There were statistically significant differences in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels among early, mid, and late pregnancy (all P < 0.05). Single-factor analysis showed that TG in the complication group was higher than that of the non-complication group, while high-density lipoprotein cholesterol (HDL-C) was lower (both P < 0.05). Dyslipidemia was detected in 932 (95.20%) of cases in the complication group and 19 (90.48%) cases in the non-complication group, with no significant difference between the groups (P=0.630). There was also no significant difference in the incidence of adverse pregnancy outcome between the dyslipidemia and non-dyslipidemia groups (P=0.396). Multifactor analysis showed that TC, TG, HDL, and LDL-C in the first, second, or third trimesters were not risk factors for complications or adverse pregnancy outcome (P > 0.05). Correlation analysis indicated that TC, TG, HDL-C, and LDL-C in the first, second, and third trimesters of pregnancy had no significant correlation with the number of complications (First trimester: r=0.099, 0.146, -0.106, 0.137; Second trimester: r=0.027, 0.152, -0.102, 0.009; Third trimester: r=0.031, 0.191, -0.064, -0.056). CONCLUSION: The serum lipid levels of pregnant women increased significantly in the second and third trimesters. However, there was no correlation between these elevated serum lipid levels and pregnancy complications or adverse outcome.

Bidirectional Mendelian randomization to explore the causal relationships between the gut microbiota and male reproductive diseases.

Gut bacteria might play an important role in male reproductive disorders, such as male infertility and sperm abnormalities; however, their causal role is unclear. Herein, Mendelian randomization (MR)-Egger, weighted median, inverse variance weighting, Simple mode, and Weighted mode were used to test the causal relationship between gut microbes and male reproductive diseases. The MR results were validated using various metrics. The MR results were also consolidated using reverse causality speculation, conducted using two-way MR analysis and Steiger filtering. Biological function was analysed using enrichment analyses. The results suggested that eight intestinal microflorae were causally associated with male infertility. The Eubacterium oxidoreducens group was associated with an increased risk of male infertility, while the family Bacteroidaceae was negatively associated with male reproductive diseases. Eight intestinal microflorae were causally associated with abnormal spermatozoa. The family Streptococcaceae was associated with a high risk of abnormal spermatozoa, whereas the family Porphyromonadaceae was associated with a low risk of abnormal spermatozoa. No pleiotropy was observed, this study identified a high correlation between the gut flora and the likelihood of male reproductive diseases. Future research will attempt to advance microbial-focused treatments for such diseases.

Impact of slit compared with nonslit mesh in laparoscopic groin hernia repairs-A comprehensive propensity score analysis of a cohort of 611 hernias.

BACKGROUND: The slit-mesh technique for laparoscopic groin hernia repair remains controversial. We present the largest cohort of patients to date that have undergone laparoscopic hernia repair with this technique and aim to evaluate the impact of both techniques on postoperative recurrence and other secondary outcomes. METHODS: A retrospective, single-institution cohort study of patients who underwent a laparoscopic groin hernia repair over a 5.5-year period was performed. Univariate and multivariate analyses were performed to identify factors associated with recurrence, chronic pain, complications, length of stay, and operative time. A propensity score analysis also was performed. Time to recurrence was then subsequently plotted on a Kaplan-Meier survival analysis. RESULTS: In total, 611 laparoscopic groin hernia repairs (nonslit: n = 353; slit: n = 258) were reviewed. Mean follow-up duration was 6.6 months. On the multivariate analysis, body mass index was inversely correlated with recurrence (odds ratio, 0.792; 95% confidence interval, 0.656-0.956), whereas a slit mesh had lower recurrence (odds ratio, 0.228; 95% confidence interval, 0.064-0.809). In the propensity score-adjusted analysis, slit mesh remained significantly associated with reduced recurrence (adjusted odds ratio, 0.251; 95% confidence interval, 0.070-0.900), with no differences in chronic pain (adjusted odds ratio, 1.297; 95% confidence interval, 0.275-6.128) or postoperative complications (adjusted odds ratio, 1.808; 95% confidence interval, 0.429-7.620). Operative time also was reduced in the slit-mesh group (P = .009). CONCLUSIONS: The slit-mesh technique was associated with a reduced likelihood of postoperative recurrence and shorter operative time, with no impact on postoperative chronic pain or complications. A lower body mass index was also correlated with increased likelihood of postoperative recurrence.

In-situ construction of biomineralized cadmium sulfide-Rhodopseudomonas palustris hybrid system: Mechanism of synergistic light utilization.

Sulfide biomineralization is a microorganism-induced process for transforming the environmentally hazardous cadmium into useful resource utilization. This study successfully constructed cadmium sulfide nanoparticles-Rhodopseudomonas palustris (Bio-CdS NPs-R. palustris) hybrids. For the self-assembling hybrids, Bio-CdS NPs were treated as new artificial-antennas to enhance photosynthesis, especially under low light (LL). Bacterial physiological results of hybrids were significantly increased, particularly for cells under LL, with higher enhancement photon harvesting ability. The enhancement included the pigment contents, and the ratio of the peripheral light-harvesting complex Ⅱ (LH2) to light-harvesting Ⅰ (1.33 ± 0.01 under LL), leading to the improvements of light-harvesting, transfer, and antenna conversion efficiencies. Finally, the stimulated electron chain of hybrids improved bacterial metabolism with increased nicotinamide adenine dinucleotide (NADH, 174.5% under LL) and adenosine triphosphate (ATP, 41.1% under LL). Furthermore, the modified photosynthetic units were induced by the up-regulated expression of fixK, which was activated by reduced oxygen tension of the medium for hybrids. fixK up-regulated genes encoding pigments (crt, and bch) and complexes (puf, pucAB, and pucC), leading to improved light-harvesting and transfer, and transform ability. This study provides a comprehensive understanding of the solar energy utilization mechanism of in-situ semiconductor-phototrophic microbe hybrids, contributing to further theoretical insight into their practical application.

Genotype Associated With Visual Prognosis in Patients With Congenital Ectopia Lentis Following Lens Surgery: A Prospective Cohort Study.

PURPOSE: To investigate the relationship between visual prognosis and genotype in patients undergoing lens surgery for congenital ectopia lentis (EL). DESIGN: Prospective clinical cohort study. METHODS: Patients with congenital EL who underwent lens removal and intraocular lens implantation received panel-based next-generation sequencing. Patients were grouped into children and adolescents/adults based on the age at surgery. The visual prognosis, including best-corrected visual acuity (BCVA) and amblyopia, was stratified into short-term and medium to long-term. RESULTS: This study included 329 probands with congenital EL, with a median age at lens surgery of 7.00 years (interquartile range [IQR] = 5.00, 12.50 years). Children with the non-FBN1 mutation exhibited inferior medium to long-term postoperative BCVA (0.26 [IQR: 0.14, 0.33] vs 0.15 [IQR: 0.10, 0.22], P = .034) and a higher prevalence of amblyopia (44.4% vs 16.8%, P = .012) compared to those with FBN1 mutation. Multivariable analysis showed that genotype (FBN1 vs non-FBN1 mutation) was significantly associated with medium to long-term postoperative BCVA (b = -0.128, 95% CI -0.214 to -0.042, P = .004) and amblyopia (OR = 0.20, 95% CI 0.05-0.78, P = .020) in children. Further classification of FBN1 genotype did not yield significant correlations with visual prognosis. However, no significant correlation was observed between genotype and short-term visual prognosis in the children. Children with less severe EL (OR = 0.13, 95% CI 0.02-0.85, P = .033) had lower risks of amblyopia in the short-term follow-up. For adolescent and adult patients with congenital EL, those with poor preoperative BCVA and long axial length should be informed of suboptimal visual prognosis. CONCLUSIONS: Genotype significantly influences the medium to long-term visual prognosis in children with congenital EL. Genotype, along with preoperative BCVA, may assist in establishing reasonable expectations for patients regarding their visual outcomes after the lens surgery.

Reagent-free anti-fouling electrochemical immunosensor based on AL-BSA/AuNPs/PANI coating for the point-of-care detection of C-reactive protein in plasma and whole blood.

Developing the portable CRP detection technologies that are suitable for point-of-care (POC) and primary care management is of utmost importance, and advancing the electrochemical immunosensors hold promise for POC implementation. Nevertheless, non-specific adsorption of numerous interfering proteins in complex biological media contaminates immunosensors, thereby restricting the reliability in detection efficacy. In this study, a three-dimensional flower-leaf shape amyloid bovine serum albumin/gold nanoparticles/polyaniline (AL-BSA/AuNPs/PANI) coating on the surface of the electrode was developed, which demonstrated strong anti-adsorption properties against bovine serum albumin, plasma, and cells. The immunosensor exhibited a good linear relationship to CRP response, featuring a detection limit of 0.09 µg/mL, consistent with clinical reference range. In addition, the CRP immunosensor demonstrated excellent specificity in other inflammation-related proteins and commendable anti-interference performance for CRP detection in plasma and whole blood tests. Importantly, by combining the development of a USB flash disk-type portable electrochemical workstation with a reagent-free mode, the developed CRP electrochemical immunosensor delivered ideal results in clinical samples. The anti-fouling performance, sensitivity and specificity of the immunosensor, as well as its flexible test modes in clinical samples, provide important scientific basis for developing POC detection technologies of vital biomarkers in complex biological media.

Expert consensus on the multidisciplinary diagnosis and treatment of multiple ground glass nodule-like lung cancer (2024 Edition).

ABSTRACT: This expert consensus reviews current literature and provides clinical practice guidelines for the diagnosis and treatment of multiple ground glass nodule-like lung cancer. The main contents of this review include the following: ① follow-up strategies, ② differential diagnosis, ③ diagnosis and staging, ④ treatment methods, and ⑤ post-treatment follow-up.

Breaking the Temperature Limit of Lithium-Ion Batteries With Carbon Nanotube-Based Electrodes and "Constructive Alliance" Electrolyte Strategy.

Lithium-ion batteries (LIBs) are paramount in energy storage in consumer electronics and electric vehicles. However, a narrow operating temperature range severely constrains their evolution. In this study, a wide-temperature operating LIB system is constructed utilizing carbon nanotube (CNT)-based electrodes and a "constructive alliance" electrolyte. The unique microstructure of the CNT current collector, with high electrical and thermal conductivity, accelerates the reaction kinetics of active materials at subzero temperatures and optimizes the thermal management of the entire electrode at elevated temperatures. Furthermore, a strategy employing the "constructive alliance" electrolyte is proposed, demonstrating that a simple combination of commercially available electrolytes can enhance resilience to harsh thermal conditions. Molecular dynamics simulations and density functional theory calculations reveal that the hybrid electrolyte predominantly adopts aggregate solvation structures and possesses low Li+ desolvation barriers regardless of thermal variations. Consequently, the assembled Li4Ti5O12//LiCoO2 full cell, with a negative/positive electrode material ratio of 1.2, exhibits outstanding electrochemical performance in the wide temperature range of -40 and 60 °C. This innovative strategy overcomes challenges in wide-temperature electrolyte research and offers promise for next-generation wide-temperature LIBs.

Constrained motion of self-propelling eccentric disks linked by a spring.

It has been supposed that the interplay of elasticity and activity plays a key role in triggering the non-equilibrium behaviors in biological systems. However, the experimental model system is missing to investigate the spatiotemporally dynamical phenomena. Here, a model system of an active chain, where active eccentric-disks are linked by a spring, is designed to study the interplay of activity, elasticity, and friction. Individual active chain exhibits longitudinal and transverse motions; however, it starts to self-rotate when pinning one end and self-beat when clamping one end. In addition, our eccentric-disk model can qualitatively reproduce such behaviors and explain the unusual self-rotation of the first disk around its geometric center. Furthermore, the structure and dynamics of long chains were studied via simulations without steric interactions. It was found that a hairpin conformation emerges in free motion, while in the constrained motions, the rotational and beating frequencies scale with the flexure number (the ratio of self-propelling force to bending rigidity), χ, as ∼(χ)4/3. Scaling analysis suggests that it results from the balance between activity and energy dissipation. Our findings show that topological constraints play a vital role in non-equilibrium synergy behaviors.

Renal denervation alleviates vascular remodeling in spontaneously hypertensive rats by regulating perivascular adipose tissue.

Vascular remodeling is the main pathological process that causes the damage of the target organ of hypertension. Perivascular adipose tissue (PVAT) surrounds blood vessels and plays a key role in the pathogenesis of various cardiovascular diseases. This study aimed to investigate the effects of renal denervation (RDN) on hypertensive vascular remodeling and to elucidate the role of PVAT in this process. Male spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rat were selected. Aortic vascular remodeling was evaluated using hematoxylin and eosin (H&E) staining and Masson's trichrome staining. Morphological changes in the PVAT were observed through H&E and Oil Red O staining. Dihydroethidium was used to measure oxidative stress levels in PVAT, while western blot analysis was used to determine the expression levels of proteins associated with vascular remodeling. The results showed that the aortic medial thickness, media thickness/lumen diameter, collagen volume fraction, and reactive oxygen species (ROS) level in PVAT were significantly higher in the SHR group than in the WKY group. The indexes mentioned above were lower in the SHR-RDN group than in the SHR group. H&E staining revealed that fat droplets in PVAT in the SHR-RDN group became smaller and browning occurred. Moreover, the protein expression of uncoupling protein-1 (UCP-1) and neuregulin 4 (Nrg4) was significantly increased in the SHR-RDN group. In addition, the expression of adiponectin increased and the expression of leptin decreased in the SHR-RDN group compared to the SHR group. In conclusion, RDN can relieve hypertensive vascular remodeling, which may be associated with PVAT.

Engineering psychrophilic polymerase for nanopore long-read sequencing.

Unveiling the potential application of psychrophilic polymerases as candidates for polymerase-nanopore long-read sequencing presents a departure from conventional choices such as thermophilic Bacillus stearothermophilus (Bst) renowned for its limitation in temperature and mesophilic Bacillus subtilis phage (phi29) polymerases for limitations in strong exonuclease activity and weak salt tolerance. Exploiting the PB-Bst fusion DNA polymerases from Psychrobacillus (PB) and Bacillus stearothermophilus (Bst), our structural and biochemical analysis reveal a remarkable enhancement in salt tolerance and a concurrent reduction in exonuclease activity, achieved through targeted substitution of a pivotal functional domain. The sulfolobus 7-kDa protein (Sso7d) emerges as a standout fusion domain, imparting significant improvements in PB-Bst processivity. Notably, this study elucidates additional functional sites regulating exonuclease activity (Asp43 and Glu45) and processivity using artificial nucleotides (Glu266, Gln283, Leu334, Glu335, Ser426, and Asp430). By disclosing the intricate dynamics in exonuclease activity, strand displacement, and artificial nucleotide-based processivity at specific functional sites, our findings not only advance the fundamental understanding of psychrophilic polymerases but also provide novel insights into polymerase engineering.

Nomogram for predicting invasive lung adenocarcinoma in small solitary pulmonary nodules.

Background: This study aimed to construct a clinical prediction model and nomogram to differentiate invasive from non-invasive pulmonary adenocarcinoma in solitary pulmonary nodules (SPNs). Method: We analyzed computed tomography and clinical features as well as preoperative biomarkers in 1,106 patients with SPN who underwent pulmonary resection with definite pathology at Qilu Hospital of Shandong University between January 2020 and December 2021. Clinical parameters and imaging characteristics were analyzed using univariate and multivariate logistic regression analyses. Predictive models and nomograms were developed and their recognition abilities were evaluated using receiver operating characteristic (ROC) curves. The clinical utility of the nomogram was evaluated using decision curve analysis (DCA). Result: The final regression analysis selected age, carcinoembryonic antigen, bronchus sign, lobulation, pleural adhesion, maximum diameter, and the consolidation-to-tumor ratio as associated factors. The areas under the ROC curves were 0.844 (95% confidence interval [CI], 0.817-0.871) and 0.812 (95% CI, 0.766-0.857) for patients in the training and validation cohorts, respectively. The predictive model calibration curve revealed good calibration for both cohorts. The DCA results confirmed that the clinical prediction model was useful in clinical practice. Bias-corrected C-indices for the training and validation cohorts were 0.844 and 0.814, respectively. Conclusion: Our predictive model and nomogram might be useful for guiding clinical decisions regarding personalized surgical intervention and treatment options.

Prognostic and clinicopathological significance of tertiary lymphoid structure in non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the primary reason for cancer-related deaths globally. Tertiary lymphoid structure (TLS) is an organized collection of immune cells acquired in non-physiological, non-lymphoid tissues. High expression of TLS in tumor tissues is generally associated with better prognosis. This research aimed to investigate the prognostic and clinicopathological significance of TLS in patients with NSCLC. METHODS: A comprehensive literature search was conducted based on Pubmed, EMBASE, and Cochrane Library databases to identify eligible studies published up to December 8, 2023. The prognostic significance and clinicopathological value of TLS in NSCLC were evaluated by calculating the combined hazard ratios (HRs) and odds ratios (ORs) and their 95% confidence intervals (CIs). Following that, additional analyses, including subgroup analysis and sensitivity analysis, were conducted. RESULTS: This meta-analysis evaluated the prognostic and clinicopathological significance of TLS in 10 studies involving 1,451 patients with NSCLC. The results revealed that the high levels of TLS were strongly associated with better overall survival (OS) (HR = 0.48, 95% CI: 0.35-0.66, p < 0.001), disease-free survival (DFS)/recurrence-free survival (RFS) (HR = 0.37, 95% CI: 0.24-0.54, p < 0.001), and disease-specific survival (DSS) (HR = 0.45, 95% CI: 0.30-0.68, p < 0.001) in NSCLC patients. In addition, the increased expression of TLS was closely related to the Tumor Node Metastasis (TNM) stage of tumors (OR = 0.71, 95% CI: 0.51-1.00, p < 0.05) and neutrophil-lymphocyte ratio (NLR) (OR = 0.33, 95% CI: 0.17-0.62, p < 0.001). CONCLUSIONS: The results revealed that highly expressed TLS is closely associated with a better prognosis in NSCLC patients. TLS may serve as a novel biomarker to predict the prognosis of NSCLC patients and guide the clinical treatment decisions.

Peptidyl-prolyl isomerase F as a prognostic biomarker associated with immune infiltrates and mitophagy in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is among the most prevalent malignancies worldwide, with unfavorable treatment outcomes. Peptidyl-prolyl isomerase F (PPIF) is known to influence the malignancy traits of tumor progression by modulating the bioenergetics and mitochondrial permeability in cancer cells; however, its role in LUAD remains unclear. Our study seeks to investigate the clinical significance, tumor proliferation, and immune regulatory functions of PPIF in LUAD. Methods: The expression of PPIF in LUAD tissues and cells was assessed using bioinformatics analysis, immunohistochemistry (IHC), and Western blotting. Survival curve analysis was conducted to examine the prognostic association between PPIF expression and LUAD. The immunomodulatory role of PPIF in LUAD was assessed through the analysis of PPIF expression and immune cell infiltration. A series of gain- and loss-of-function experiments were conducted on PPIF to investigate its biological functions in LUAD both in vitro and in vivo. The mechanisms underlying PPIF's effects on LUAD were delineated through functional enrichment analysis and Western blotting assays. Results: PPIF exhibited overexpression in LUAD tissues compared to normal controls. Survival curve analysis revealed that patients with LUAD exhibiting higher PPIF expression demonstrated decreased overall survival and a shorter progression-free interval. PPIF was implicated in modulating immune cell infiltration, particularly in regulating the T helper 1-T helper 2 cell balance. Functionally, PPIF was discovered to promote tumor cell proliferation and advance cell-cycle progression. Furthermore, PPIF could impede mitophagy by targeting the FOXO3a/PINK1-Parkin signaling pathway. Conclusions: The findings of this study indicate that the prognosis-related gene PPIF may have a significant role in the regulation of LUAD cell proliferation, tumor-associated immune cell infiltration, and mitophagy, and thus PPIF may be a promising therapeutic target of LUAD.