Aerosol inhalation of total ginsenosides repairs acute lung injury and inhibits pulmonary fibrosis through SMAD2 signaling-mediated mechanism.

BACKGROUND: Pulmonary fibrosis (PF) is a progressive lung disease caused by previous acute lung injury (ALI), but there is currently no satisfactory therapy available. Aerosol inhalation of medicine is an effective way for treating PF. Total ginsenosides (TG) shows potential for the treatment of ALI and PF, but the effects of inhaled TG remain unclear. PURPOSE: To determine the therapeutic effects of TG in ALI and PF, to assess the superiority of the inhaled form of TG over the routine form, and to clarify the mechanism of action of inhaled TG. METHODS: Ultrahigh-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry (UPLC-QE-MS) was applied to determine the chemoprofile of TG. A mouse model of ALI and PF was established to evaluate the effects of inhaled TG by using bronchoalveolar lavage fluid (BALF) analysis, histopathological observation, hydroxyproline assay, and immunohistochemical analysis. Primary mouse lung fibroblasts (MLF) and human lung fibroblast cell line (HFL1) were applied to determine the in vitro effects and mechanism of TG by using cell viability assay, quantitative real time PCR (qPCR) assay, and western blot (WB) analysis. RESULTS: The UPLC-QE-MS results revealed the main types of ginsenosides in TG, including Re (14.15 ± 0.42%), Rd (8.42 ± 0.49%), Rg1 (6.22 ± 0.42%), Rb3 (3.28 ± 0.01%), Rb2 (3.09 ± 0.00%), Rc (2.33 ± 0.01%), Rg2 (2.09 ± 0.04%), Rb1 (1.43 ± 0.24%), and Rf (0.13 ± 0.06%). Inhaled TG, at dosages of 10, 20, and 30 mg/kg significantly alleviated both ALI and PF in mice. Analyses of BALF and HE staining revealed that TG modulated the levels of IFN-γ, IL-1ß, and TGF-ß1, reduced inflammatory cell infiltration, and restored the alveolar architecture of the lung tissues. Furthermore, HE and Masson's trichrome staining demonstrated that TG markedly decreased fibroblastic foci and collagen fiber deposition, evidenced by the reduction of blue-stained collagen fibers. Hydroxyproline assay and immunohistochemical analyses indicated that TG significantly decreased hydroxyproline level and down-regulated the expression of Col1a1, Col3a1, and α-sma. The inhaled administration of TG demonstrated enhanced efficacy over the oral route when comparable doses were used. Additionally, inhaled TG showed superior safety and therapeutic profiles compared to pirfenidone, as evidenced by a CCK8 assay, which confirmed that TG concentrations ranging from 20 to 120 µg/ml were non-cytotoxic. qPCR and WB analyses revealed that TG, at concentrations of 25, 50, and 100 µg/ml, significantly suppressed the phosphorylation of smad2 induced by TGF-ß1 and down-regulated the expression of fibrotic genes and proteins, including α-sma, Col1a1, Col3a1, and FN1, suggesting an anti-fibrotic mechanism mediated by the smad2 signaling pathway. In vitro, TG's safety and efficacy were also found to be superior to those of pirfenidone. CONCLUSIONS: This study demonstrates, for the first time, the therapeutic efficacy of inhaled TG in treating ALI and PF. Inhaled TG effectively inhibits inflammation and reduces collagen deposition, with a particular emphasis on its role in modulating the Smad2 signaling pathway, which is implicated in the anti-fibrotic mechanism of TG. The study also highlights the superiority of inhaled TG over the oral route and its favorable safety profile in comparison to pirfenidone, positioning it as an ideal alternative for ALI and PF therapy.

Deciphering deep-sea chemosynthetic symbiosis by single-nucleus RNA-sequencing.

Bathymodioline mussels dominate deep-sea methane seep and hydrothermal vent habitats and obtain nutrients and energy primarily through chemosynthetic endosymbiotic bacteria in the bacteriocytes of their gill. However, the molecular mechanisms that orchestrate mussel host-symbiont interactions remain unclear. Here, we constructed a comprehensive cell atlas of the gill in the mussel Gigantidas platifrons from the South China Sea methane seeps (1100 m depth) using single-nucleus RNA-sequencing (snRNA-seq) and whole-mount in situ hybridisation. We identified 13 types of cells, including three previously unknown ones, and uncovered unknown tissue heterogeneity. Every cell type has a designated function in supporting the gill's structure and function, creating an optimal environment for chemosynthesis, and effectively acquiring nutrients from the endosymbiotic bacteria. Analysis of snRNA-seq of in situ transplanted mussels clearly showed the shifts in cell state in response to environmental oscillations. Our findings provide insight into the principles of host-symbiont interaction and the bivalves' environmental adaption mechanisms.

Correlation between Circle of Willis Configuration and Intracranial Arterial Dolichoectasia, and Genetic Contributions.

OBJECTIVES: Intracranial arterial dolichoectasia (IADE) is characterized by the dilation, elongation, and tortuosity of intracranial arteries. We aimed to investigate the association between variations of the Circle of Willis (COW) and IADE in the general population, as well as estimate the genetic correlation between COW variations and IADE. METHODS: A total of 981 individuals from a population-based cohort were included. Brain magnetic resonance angiography was performed to assess COW variants and measure the diameters of intracranial arteries. IADE was defined as a total intracranial volume-adjusted diameter ≥ 2 standard deviations. Logistic regression models were used to analyze the association between COW variations and IADE. The heritability and genetic correlation were estimated using genome-wide complex trait analysis (GCTA) based on single nucleotide polymorphism (SNP) array data. RESULTS: The prevalence of IADE was 6.2%. Hypoplastic/absent A1 segments were associated with an increase in contralateral ICA diameter (ß ± SE, 0.279 ± 0.049; p = 0.001) and a decrease in ipsilateral ICA diameter (ß ± SE, -0.300 ± 0.050; p = 0.001). Fetal-type posterior cerebral artery (FTP) was associated with a larger ICA diameter (ß ± SE, 0.326 ± 0.048; p = 0.001) and a smaller BA diameter (ß ± SE, -0.662 ± 0.043; p = 0.001). FTP revealed a positive genetic correlation with ICA dilation (rG = 0.259 ± 0.175; p = 0.0009) and a negative genetic correlation with BA dilation (rG = -0.192 ± 0.153, p = 0.015). CONCLUSIONS: There was an association between COW variations and larger intracranial arterial diameters in the general population. Genetic factors may play a role in the development of intracranial arterial dilation and the formation of COW variants.

[Retracted] Cognitive improvements and reduction in amyloid plaque deposition by saikosaponin D treatment in a murine model of Alzheimer's disease.

[This retracts the article DOI: 10.3892/etm.2020.8760.].

Predominance of hyperprogression in mucosal melanoma during anti-PD-1 monotherapy treatment.

BACKGROUND: A minority subset of immunotherapy patients manifests hyperprogressive disease (HPD), with the disparity in melanoma subtypes yet to be reported. This study aimed to delineate the proportion and prognosis of HPD in patients receiving anti-PD-1 monotherapy and to identify patient with HPD clinical characteristics across melanoma subtypes to inform clinical decision making. METHODS: Utilizing 4 established HPD definitions, the incidence of HPD in patients with advanced melanoma on anti-PD-1 monotherapy was determined. The incidence rates and prognostic abilities of various HPD definitions were compared to elect the most effective one. This facilitated a comparative analysis of subtypes and clinical features between patients with HPD and traditional progression. RESULTS: A total of 262 patients with advanced melanoma treated with anti-PD-1 monotherapy from 5 prospectively registered clinical trials were included in the study. The objective response rate (ORR) and disease control rate (DCR) was 21% and 58%, respectively, with 42% showcasing progression disease. The HPD incidences by 4 definitions were 13.2%, 16.8%, 10.8%, and 28.2%. All definitions effectively segregated HPD patients, with significantly poorer outcome than other progressive patients. The Delta TGR > 100 definition was the most indicative of a reduced overall survival, corroborated by the highest hazard ratio and statistical significance. The number of metastatic organs over 2 is a risk factor for HPD (OR = 4.18, P = .0103). Mucosal melanoma was the HPD prevalent subtype (OR = 3.13, P = .0489) in multivariable analysis, which is also indicated by RECIST criteria (P = .005). CONCLUSION: A delta TGR exceeding 100 best identified HPD patients in the advanced melanoma population treated with anti-PD-1 monotherapy. Hyperprogression was notably prevalent in mucosal melanoma patients with multiple metastatic organs. Caution against HPD is warranted when applying anti-PD-1 monotherapy in mucosal subtype.

Assessments of various precipitation product performances and disaster monitoring utilities over the Tibetan Plateau.

The Tibetan Plateau, often referred to as Asia's water tower, is a focal point for studying spatiotemporal changes in water resources amidst global warming. Precipitation is a crucial water resource for the Tibetan Plateau. Precipitation information holds significant importance in supporting research on the Tibetan Plateau. In this study, we estimate the performance and applicability of Climate Prediction Center Merged Analysis of Precipitation (CMAP), Integrated Multi-Satellite Retrievals for Global Precipitation Measurement (IMERG), Global Land Data Assimilation System (GLDAS), and Global Precipitation Climatology Project (GPCP) precipitation products for estimating precipitation and different disaster scenarios (including extreme precipitation, drought, and snow) across the Tibetan Plateau. Extreme precipitation and drought indexes are employed to describe extreme precipitation and drought conditions. We evaluated the performance of various precipitation products using daily precipitation time series from 2000 to 2014. Statistical metrics were used to estimate and compare the performances of different precipitation products. The results indicate that (1) Both CMAP and IMERG showed higher fitting degrees with gauge precipitation observations in daily precipitation. Probability of detection, False Alarm Ratio, and Critical Success Index values of CMAP and IMERG were approximately 0.42 to 0.72, 0.38 to 0.56, and 0.30 to 0.42, respectively. Different precipitation products presented higher daily average precipitation amount and frequency in southeastern Tibetan Plateau. (2) CMAP and GPCP precipitation products showed relatively great and poor performance, respectively, in predicting daily and monthly precipitation on the plateau. False alarms might have a notable impact on the accuracy of precipitation products. (3) Extreme precipitation amount could be better predicted by precipitation products. Extreme precipitation day could be badly predicted by precipitation products. Different precipitation products showed that the bias of drought estimation increased as the time scale increased. (4) GLDAS series products might have relatively better performance in simulating (main range of RMSE: 2.0-4.5) snowfall than rainfall and sleet in plateau. G-Noah demonstrated slightly better performance in simulating snowfall (main range of RMSE: 1.0-2.1) than rainfall (main range of RMSE: 2.0-3.8) and sleet (main range of RMSE: 1.5-3.8). This study's findings contribute to understanding the performance variations among different precipitation products and identifying potential factors contributing to biases within these products. Additionally, the study sheds light on disaster characteristics and warning systems specific to the Tibetan Plateau.

Comparison of TyG and Newly TyG Related Indicators for Chronic Kidney Diseases Estimation in a Chinese Population.

Background: Obesity and insulin resistance (IR) are positively associated with chronic kidney disease (CKD). Previous studies have identified triglyceride-glucose index (TyG) as a valuable surrogate of insulin resistance. Recently, new indicators combining TyG and simple anthropometric indices have emerged, The objective of this study was to assess the diagnostic accuracy of TyG and newly TyG related indicators in detecting CKD and explore which indices were superior in associating with CKD in Chinese population. Methods: Correlation test, logistic regression analysis, and receiver operating characteristic (ROC) analyses were used to evaluate the optimal cut-off and value of TyG, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), TyG-waist to height ratio (TyG-WHtR) for predicting CKD. Results: TyG-WHtR, TyG-WC, and TyG-BMI correlated with several risk factors for CKD. After adjusting for confounders, TyG-WHtR and TyG-WC remained significantly associated with CKD, while TyG-BMI did not. The highest quartiles of TyG-WHtR and TyG-WC had 1.95- and 1.91-fold increased risk of CKD than the lowest quartiles (P<0.05). TyG-WHtR had the largest AUC (0.687) for CKD detection, followed by TyG-WC (0.669), TyG (0.652), and TyG-BMI (0.648). A united model that involved TyG-WHtR and other risk variables had higher predictive performance (AUC=0.791) than a single TyG related indicator. However, TyG had the highest OR (2.713, 95% CI, 1.446-5.090) for reduced eGFR in the fully adjusted model. A united model that involved TyG and WHtR separately had stronger predictive ability (AUC: 0.794) than the model that involved TyG-WHtR individually (AUC:0.791). Conclusion: This study found that TyG-WHtR had a better diagnostic value in the diagnosis of CKD, compared to other TyG related indicators, but none of the TyG related indicators showed a stronger association with CKD than TyG. Further research and more refined algorithms are needed to verify these new indicators.

Genome-Wide Mendelian Randomization Study Reveals Druggable Genes for Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease (CSVD) is a group of neurological disorders that affect the small blood vessels within the brain, for which no effective treatments are currently available. We conducted a Mendelian randomization (MR) study to identify candidate therapeutic genes for CSVD. METHODS: We retrieved genome-wide association study data from 6 recently conducted, extensive investigations focusing on CSVD magnetic resonance imaging markers and performed a 2-sample MR analysis to assess the potential causal effects of gene expression and protein level within druggable genes on CSVD in blood and brain tissues. Colocalization analyses and repeat studies were undertaken to verify the relationship. Additionally, mediation analysis was conducted to explore the potential mechanisms involving druggable genes and known risk factors for CSVD. Finally, phenome-wide MR analyses were applied to evaluate the potential adverse effects related to the identified druggable genes for CSVD treatment. RESULTS: Overall, 5 druggable genes consistently showed associations with CSVD in MR analyses across both the discovery and validation cohorts. Notably, the ALDH2 and KLHL24 genes were identified as associated with CSVD in both blood and brain tissues, whereas the genes ADRB1, BTN3A2, and EFEMP1 were exclusively detected in brain tissue. Moreover, mediation analysis elucidated the proportion of the total effects mediated by CSVD risk factors through candidate druggable genes, which ranged from 5.5% to 18.5%, and offered potential explanations for the observed results. A comprehensive phenome-wide MR analysis further emphasized both the therapeutic benefits and potential side effects of targeting these candidate druggable genes. CONCLUSIONS: This study provides genetic evidence supporting the potential therapeutic benefits of targeting druggable genes for treating CSVD, which will be useful for prioritizing CSVD drug development.

A comprehensive review of new small molecule drugs approved by the FDA in 2022: Advance and prospect.

In 2022, the U.S. Food and Drug Administration approved a total of 16 marketing applications for small molecule drugs, which not only provided dominant scaffolds but also introduced novel mechanisms of action and clinical indications. The successful cases provide valuable information for optimizing efficacy and enhancing pharmacokinetic properties through strategies like macrocyclization, bioequivalent group utilization, prodrug synthesis, and conformation restriction. Therefore, gaining an in-depth understanding of the design principles and strategies underlying these drugs will greatly facilitate the development of new therapeutic agents. This review focuses on the research and development process of these newly approved small molecule drugs including drug design, structural modification, and improvement of pharmacokinetic properties to inspire future research in this field.

In vivo CRISPR-Cas9 expression in Candida glabrata, Candida bracarensis, and Candida nivariensis: A versatile tool to study chromosomal break repair.

The CRISPR-Cas9 system is extremely useful for genome editing in many species, including the model yeast Saccharomyces cerevisiae, and other yeast species. We have previously reported the use of an inducible CRISPR-Cas9 system in Candida glabrata, which allows genome editing but also the study of double-strand break (DSB) repair. We report, in this study, a comparable system for C. glabrata, relying on a new plasmid, which is more stable than the previous one. We also report the use of this plasmid to induce DSBs in two additional human pathogens, Candida bracarensis and Candida nivariensis. We examine lethality induced by an in vivo DSB in the three species and describe the different types of nonhomologous end-joining (NHEJ) events detected in these three pathogens.

Epitranscriptomic m5C methylation of SARS-CoV-2 RNA regulates viral replication and the virulence of progeny viruses in the new infection.

While the significance of N6-methyladenosine (m6A) in viral regulation has been extensively studied, the functions of 5-methylcytosine (m5C) modification in viral biology remain largely unexplored. In this study, we demonstrate that m5C is more abundant than m6A in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and provide a comprehensive profile of the m5C landscape of SARS-CoV-2 RNA. Knockout of NSUN2 reduces m5C levels in SARS-CoV-2 virion RNA and enhances viral replication. Nsun2 deficiency mice exhibited higher viral burden and more severe lung tissue damages. Combined RNA-Bis-seq and m5C-MeRIP-seq identified the NSUN2-dependent m5C-methylated cytosines across the positive-sense genomic RNA of SARS-CoV-2, and the mutations of these cytosines enhance RNA stability. The progeny SARS-CoV-2 virions from Nsun2 deficiency mice with low levels of m5C modification exhibited a stronger replication ability. Overall, our findings uncover the vital role played by NSUN2-mediated m5C modification during SARS-CoV-2 replication and propose a host antiviral strategy via epitranscriptomic addition of m5C methylation to SARS-CoV-2 RNA.

Genomic anatomy of homozygous XX females and YY males reveals early evolutionary trajectory of sex-determining gene and sex chromosomes in Silurus fishes.

Sex chromosomes display remarkable diversity and variability among vertebrates. Compared with research on the X/Y and Z/W chromosomes, which have long evolutionary histories in mammals and birds, studies on the sex chromosomes at early evolutionary stages are limited. Here, we precisely assembled the genomes of homozygous XX female and YY male Lanzhou catfish (Silurus lanzhouensis) derived from an artificial gynogenetic family and a self-fertilized family, respectively. Chromosome 24 (Chr24) was identified as the sex chromosome based on resequencing data. Comparative analysis of the X and Y chromosomes showed an approximate 320 kb Y-specific region with a Y-specific duplicate of anti-Mullerian hormone type-II receptor (amhr2y), which is consistent with findings in two other Silurus species but on different chromosomes (Chr24 of S. meridionalis and Chr5 of S. asotus). Deficiency of amhr2y resulted in male-to-female sex reversal, indicating that amhr2y plays a male-determining role in S. lanzhouensis. Phylogenetic analysis and comparative genomics revealed that the common sex-determining gene amhr2y was initially translocated to Chr24 of the Silurus ancestor along with the expansion of transposable elements. Chr24 was maintained as the sex chromosome in S. meridionalis and S. lanzhouensis, whereas a sex-determining region transition triggered sex chromosome turnover from Chr24 to Chr5 in S. asotus. Additionally, gene duplication, translocation, and degeneration were observed in the Y-specific regions of Silurus species. These findings present a clear case for the early evolutionary trajectory of sex chromosomes, including sex-determining gene origin, repeat sequence expansion, gene gathering and degeneration in sex-determining region, and sex chromosome turnover.

Research Progress on Detection of New Psychoactive Substance Piperazines in vivo.

Piperazines are a class of new psychoactive substances with hallucinogenic effects that affect the central nervous system by affecting the level of monoamine neurotransmitters. Abuse of piperazines will produce stimulating and hallucinogenic effects, accompanied by headache, dizziness, anxiety, insomnia, vomiting, chest pain, tachycardia, hypertension and other adverse reactions, and may even cause cardiovascular diseases and multiple organ failure and lead to death, seriously affecting human physical and mental health and public safety. The abuse of new psychoactive substance piperazines has attracted extensive attention from the international community. The study of its pharmacological toxicology and analytical methods has become a research hotspot in the field of forensic medicine. This paper reviews the in vivo processes, sample treatment and analytical methods of existing piperazines, in order to provide reference for forensic identification.

Development of a Predictive Nomogram for Intra-Hospital Mortality in Acute Ischemic Stroke Patients Using LASSO Regression.

Background and Purpose: Ischemic stroke is a leading cause of mortality and disability globally, necessitating accurate prediction of intra-hospital mortality (IHM) for improved patient care. This study aimed to develop a practical nomogram for personalized IHM risk prediction in ischemic stroke patients. Methods: A retrospective study of 422 ischemic stroke patients (April 2020 - December 2021) from Chongqing Medical University's First Affiliated Hospital was conducted, with patients divided into training (n=295) and validation (n=127) groups. Data on demographics, comorbidities, stroke risk factors, and lab results were collected. Stroke severity was assessed using NIHSS, and stroke types were classified by TOAST criteria. Least absolute shrinkage and selection operator (LASSO) regression was employed for predictor selection and nomogram construction, with evaluation through ROC curves, calibration curves, and decision curve analysis. Results: LASSO regression and multivariate logistic regression identified four independent IHM predictors: age, admission NIHSS score, chronic obstructive pulmonary disease (COPD) diagnosis, and white blood cell count (WBC). A highly accurate nomogram based on these variables exhibited excellent predictive performance, with AUCs of 0.958 (training) and 0.962 (validation), sensitivities of 93.2% and 95.7%, and specificities of 93.1% and 90.9%, respectively. Calibration curves and decision curve analysis validated its clinical applicability. Conclusion: Age, admission NIHSS score, COPD history, and WBC were identified as independent IHM predictors in ischemic stroke patients. The developed nomogram demonstrated high predictive accuracy and practical utility for mortality risk estimation. External validation and prospective studies are warranted for further confirmation of its clinical efficacy.

Physicochemical properties and flavor substances analyses of refined beef tallow with dry fractionation treatment.

Dry fractionation represents a significant technique for separation of diverse fractions from beef tallow. The objective of this study was to undertake a systematic investigation of alterations in physicochemical properties, crystallization behavior, thermal properties, and flavor compounds that occur during the beef tallow dry fractionation process. The solid component yielded at 40, 30, and 15 °C were 44.88%, 33.72%, and 13.04% respectively, with an 8.36% liquid content at 15 °C, which was consistent with the characteristics of saturated fatty acids content. The ß - ß' transformation in the dry fractionation process was clearly revealed by X-ray diffraction. Differential scanning calorimetry curves exhibited alterations in exothermic and endothermic peak, as well as enthalpy. Electronic nose identified short-chain compounds, aldehydes, ketones, and nitrogen-containing substances as flavor compounds. Volatile compounds were quantified using HS-SPME-GC-MS. Overall, dry fractionation produces beef tallow fractionated compounds with diverse physicochemical properties and aromatic-active substances, thereby expanding its potential utilization.

Nitrogen removal performance and mechanism in constructed wetlands under saline conditions: Role of Canna indica inoculated with Piriformospora indica.

The phytopromotional root endophytic fungus Piriformospora indica was introduced into the wetland plant Canna indica L. to explore its impact on nitrogen (N) removal in constructed wetlands (CWs) to treat normal and saline (0.9 % NaCl) wastewater. P. indica colonization increased total nitrogen, NH4+-N, and NO3--N removal efficiencies under normal and saline conditions, with NO3--N removal rates significantly increasing by 17.5 % under saline conditions (P<0.05). N removal by plant uptake improved by 26.1 % and 27.7 % under normal and saline conditions due to P. indica-mediated growth-promoting effects. Salt-tolerant denitrifiers and nitrifiers guaranteed the dominant role of microbial degradation in N removal under saline conditions. P. indica inoculation considerably improved the contribution of Nocardioides and Nitrosomnas to dissimilatory/assimilatory nitrate reduction and nitrification genes, respectively. These findings elucidate the mechanisms and potential applications of P. indica-mediated phytoremediation in practical wastewater treatment under varying salty conditions.

The impact of chronic obstructive pulmonary disease on the risk of immune-related pneumonitis in lung cancer patients undergoing immunotherapy: a systematic review and meta-analysis.

BACKGROUND: Lung cancer, a leading cause of cancer mortality, poses significant treatment challenges. The use of immune checkpoint inhibitors (ICIs) has revolutionized therapy, but it is associated with immune-related pneumonitis (IRP). This study systematically reviews and analyzes the impact of Chronic Obstructive Pulmonary Disease (COPD) on the risk of IRP in lung cancer patients undergoing immunotherapy. METHODS: Adhering to PRISMA guidelines and using the PICO framework, a comprehensive search across PubMed, Embase, Web of Science, and the Cochrane Library was conducted. Inclusion criteria encompassed peer-reviewed studies involving lung cancer patients treated with ICIs, comparing those with and without COPD. The primary outcome was the incidence and risk of IRP. The Newcastle-Ottawa Scale evaluated study quality. The effect size was calculated using random or fixed-effects models based on the observed heterogeneity. We assessed the heterogeneity between studies and conducted a sensitivity analysis. RESULTS: The search identified 1026 articles, with six meeting the criteria for inclusion. Studies varied in design and geography, predominantly retrospective cohort studies. Patients with COPD had an increased risk of IRP (OR = 1.54, 95% CI [1.24, 1.92, P < 0.01). Subgroup analysis based on radiation therapy exposure (< 40% and ≥ 40%) also indicated a heightened IRP risk in COPD patients. Sensitivity analysis affirmed the robustness of the results, and publication bias was not significant. CONCLUSIONS: Lung cancer patients with COPD undergoing immunotherapy have a significantly increased risk of developing IRP. This highlights the necessity for vigilant monitoring and individualized treatment strategies to improve the safety and effectiveness of immunotherapy in this group.

Transcriptomic responses and evolutionary insights of deep-sea and shallow-water mussels under high hydrostatic pressure condition.

Marine mussels inhabit a wide range of ocean depths, necessitating unique adaptations to cope with varying hydrostatic pressures. This study investigates the transcriptomic responses and evolutionary adaptations of the deep-sea mussel Gigantidas platifrons and the shallow-water mussel Mytilus galloprovincialis to high hydrostatic pressure (HHP) conditions. By exposing atmospheric pressure (AP) acclimated G. platifrons and M. galloprovincialis to HHP, we aim to simulate extreme environmental challenges and assess their adaptive mechanisms. Through comparative transcriptomic analysis, we identified both conserved and species-specific mechanisms of adaptation, with a notable change in gene expression associated with immune system, substance transport, protein ubiquitination, apoptosis, lipid metabolism and antioxidant processes in both species. G. platifrons demonstrated an augmented lipid metabolism, whereas M. galloprovincialis exhibited a dampened immune function. Additionally, the expressed pattern of deep-sea mussel G. platifrons were more consistent than shallow-water mussel M. galloprovincialis under hydrostatic pressures changed conditions which corresponding the long-term living stable deep-sea environment. Moreover, evolutionary analysis pinpointed positively selected genes in G. platifrons that are linked to transmembrane transporters, DNA repair and replication, apoptosis, ubiquitination which are important to cell structural integrity, substances transport, and cellular growth regulation. This indicates a specialized adaptation strategy in G. platifrons to cope with the persistent HHP conditions of the deep sea. These results offer significant insights into the molecular underpinnings of mussel adaptation to varied hydrostatic conditions and enhance our comprehension of the evolutionary forces driving their depth-specific adaptations.