Superiority of opioid free anesthesia with regional block over opioid anesthesia with regional block in the quality of recovery after retroperitoneiscopic renal surgery: a randomized controlled trial.

BACKGROUND: Opioids are the main analgesic drugs used in the perioperative period, but they often have various adverse effects. Recent studies have shown that quadratus lumborum block (QLB) has an opioid sparing effect. The aim of this study was to further evaluate the effect of opioid-free anesthesia (OFA) combined with regional block on the quality of recovery in patients undergoing retroperitoneoscopic renal surgery. METHODS: Sixty patients undergoing elective retroperitoneoscopic renal surgery were divided into the opioid-free anesthesia with quadratus lumborum block group (OFA group, N.=30) and opioid anesthesia with quadratus lumborum block group (OA group, N.=30) using the random number table method. The main outcome measures were the quality of recovery assessed by Quality of Recover-40 (QoR-40) at the 24th postoperative hour. Secondary outcomes were postoperative pain score, postoperative opioid consumption, postoperative nausea and vomiting, time to ambulate, and time to readiness for discharge. RESULTS: The QoR-40 score on the first postoperative day was significantly higher in the OFA group than that in the OA group (175.41±6.74 vs. 165.07±4.55; P<0.05). OFA also significantly reduced postoperative pain (P<0.05) and morphine consumption at both the 24th and 48th postoperative hour (P<0.05), as well as time to ambulate, and time to readiness for discharge (P<0.05). CONCLUSIONS: OFA with regional block is superior to opioid anesthesia with regional block in the quality of recovery after retroperitoneiscopic renal surgery.

Targeting TNFRSF25 by agonistic antibodies and multimeric TL1A proteins co-stimulated CD8+ T cells and inhibited tumor growth.

BACKGROUND: Tumor necrosis factor receptor superfamily 25 (TNFRSF25) is a T-cell co-stimulatory receptor. Expression of its ligand, TNF-like cytokine 1A (TL1A), on mouse tumor cells has been shown to promote tumor regression. This study aimed to develop TNFRSF25 agonists (both antibodies (Abs) and TL1A proteins) and to investigate their potential antitumor effects. METHODS: Anti-mouse TNFRSF25 (mTNFRSF25) Abs and multimeric TL1A proteins were generated as TNFRSF25 agonists. Their agonism was assessed in luciferase reporter and T-cell co-stimulation assays, and their antitumor effects were evaluated in syngeneic mouse tumor models. TNFRSF25 expression within the tumor microenvironment and the effects of an anti-mTNFRSF25 agonistic Ab on tumor-infiltrating T cells were evaluated by flow cytometry. Cell depletion assays were used to identify the immune cell types that contribute to the antitumor effect of the anti-mTNFRSF25 Ab. The Fc gamma receptor (FcγR) dependence of TNFRSF25 agonists was assessed in an in vivo T-cell expansion model and a mouse tumor model using Fc variants and FcγR-deficient mice. RESULTS: TNFRSF25 agonists exhibited antitumor effects in syngeneic mouse tumor models without causing observed side effects. We identified an anti-mTNFRSF25 agonistic Ab, 1A6-m1, which exhibited greater antitumor activity than a higher affinity anti-TNFRSF25 Ab which engages an overlapping epitope with 1A6-m1. 1A6-m1 activated CD8+ T cells and antigen-specific T cells, leading to tumor regression; it also induced long-term antitumor immune memory. Although activating TNFRSF25 by 1A6-m1 expanded splenic regulatory T (Treg) cells, it did not influence intratumoral Treg cells. Moreover, 1A6-m1's antitumor effects required the engagement of both inhibitory FcγRIIB and activating FcγRIII. Replacing 1A6-m1's CH1-hinge region with that of human IgG2 (h2) conferred enhanced antitumor effects. Finally, we also generated multimeric human and mouse TL1A fusion proteins as TNFRSF25 agonists, and they co-stimulated CD8+ T cells and reduced tumor growth, even in the absence of Fc-FcγR interactions. CONCLUSION: Our data demonstrates the potential of activating TNFRSF25 by Abs and multimeric TL1A proteins for cancer immunotherapy and provides insights into their development astherapeutics.

Genetic predisposition to type 2 diabetes mellitus and aortic dissection: a Mendelian randomisation study.

Background: This Mendelian randomization (MR) study aimed to explore the causal relationship between the genetic predisposition to type 2 diabetes mellitus (T2DM) and aortic dissection (AD), and to assess associations with genetically predicted glycemic traits. The study sought to verify the inverse relationship between T2DM and AD using a more robust and unbiased method, building on the observational studies previously established. Materials and methods: The study employed a two-sample and multivariable MR approach to analyze genetic data from the DIAbetes Meta-ANalysis of Trans-Ethnic association studies (DIAMANTE) with 74,124 cases and 824,006 controls, and the Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC) involving up to 196,991 individuals. For AD data, FinnGen Release 10 was used, including 967 cases and 381,977 controls. The research focused on three foundational MR assumptions and controlled for confounders like hypertension. Genetic instruments were selected for their genome-wide significance, and multiple MR methods and sensitivity analyses were conducted. Results: The study revealed no significant effect of genetic predisposition to T2DM on the risk of AD. Even after adjusting for potential confounders, the results were consistent, indicating no causal relationship. Additionally, glycemic traits such as fasting glucose, fasting insulin, and HbA1c levels did not show a significant impact on AD susceptibility. The findings remained stable across various MR models and sensitivity analyses. In contrast, genetic liability to T2DM and glycemic traits showed a significant association with coronary artery disease (CAD), aligning with the established understanding. Conclusion: Contrary to previous observational studies, this study concludes that genetic predisposition to T2DM does not confer protection against AD. These findings underscore the imperative for further research, particularly in exploring the preventative potential of T2DM treatments against AD and to facilitate the development of novel therapeutic interventions.

Characterisation of the novel HLA-A*24:630 allele by sequencing-based typing.

HLA-A*24:630 differs from HLA-A*24:20:01:01 by one nucleotide substitution in codon 131 in exon 3.

Correlation between obesity and early vascular aging in middle-aged and young adult health check-up populations. / ä¸­é’å¹´å¥åº·ä½“æ£€äººç¾¤è‚¥èƒ–ä¸Žæ—©å‘è¡€ç®¡è€åŒ–çš„ç›¸å ³æ€§.

OBJECTIVES: The obesity rate among middle-aged and young adults in China is increasing annually, and the incidence of cardiovascular diseases is becoming more prevalent in younger populations. However, it has not yet been reported whether obesity is associated with early vascular aging (EVA). This study aims to explore the correlation between obesity and EVA in middle-aged and young adult health check-up populations, providing a reference for the prevention of cardiovascular diseases. METHODS: A total of 15 464 middle-aged and young adults aged 18-59 who completed brachial-ankle pulse wave velocity (baPWV) test in the Third Xiangya Hospital of Central South University from January to December 2020 were included. Among them, 1 965 individuals with normal blood pressure and no cardiovascular risk factors were selected as the healthy population. The baPWV thresholds for determining EVA in each age group for males and females were calculated based on the baPWV values of the healthy population. The number and percentage of individuals meeting the EVA criteria in the middle-aged and young adult health check-up populations were statistically analyzed by age and gender. The differences in obesity indicators [visceral adiposity index (VAI), body mass index (BMI), waist circumference (WC)] between the EVA and non-EVA groups for males and females were compared. Using EVA as the dependent variable, VAI, BMI, and WC were included as independent variables in a Logistic model to analyze the correlation between each obesity indicator and EVA before and after adjusting for other influencing factors. Furthermore, the correlation between each obesity indicator and EVA in each age group was analyzed. RESULTS: In the health check-up populations, the detection rate of EVA in different age groups was 1.65%-10.92% for males, and 1.16%-10.50% for females, the detection rate of EVA increased with age in both males and females. Except for the 40-<50 age group, the EVA detection rate was higher in males than in females in all other age groups. Regardless of gender, obesity indicators VAI, BMI, and WC were significantly higher in the EVA group than in the non-EVA group (all P<0.01). Before and after adjusting for other influencing factors, VAI and WC were both correlated with EVA (both P<0.05). BMI was a risk factor for EVA before adjusting for other influencing factors (P<0.01), but after adjustment, the correlation between BMI and EVA was not statistically significant (P=0.05). After adjusting for other influencing factors, the correlation between VAI and EVA was statistically significant in the 18-<40 and 50-<60 age groups (both P<0.05), while the correlation between BMI and WC with EVA was not statistically significant (both P>0.05). In the 40-<50 age group, the correlation between VAI and BMI with EVA was not statistically significant (both P>0.05), but the correlation between WC and EVA was statistically significant (P<0.01). CONCLUSIONS: VAI is closely related to the occurrence of EVA in middle-aged and young adults aged 18-<40 and 50-<60 years, while WC is closely related to the occurrence of EVA in those aged 40-<50 years.

Effects of pregabalin combined with tramadol/paracetamol on acute pain in patients with CT-guided puncture localization of pulmonary nodules.

OBJECTIVE: To investigate the effects of pregabalin combined with tramadol/paracetamol on acute pain in patients with CT-guided puncture localization of pulmonary nodules. MATERIALS AND METHODS: In this randomized, placebo-controlled and single-center study, 120 patients were allocated randomly to four groups: the control group (Group P), the pregabalin-placebo group (Group BP), the tramadol/paracetamol-placebo group (Group AP), and the pregabalin-tramadol/paracetamol group (Group AB). The primary outcome was the NRS (Numerical Rating Scale) score. Other outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), pulse oxygen saturation (SpO2), the incidence of moderate to severe pain, the analgesia recovery ratio, the incidence of adverse drug reactions and patients' satisfaction. RESULTS: No significant interaction was detected between the interventions (P = 0.752). The NRS score of the Taking pregabalin group and the Taking tramadol/paracetamol group were significantly lower than those of the Not-taking pregabalin group and the Not-taking tramadol/paracetamol group respectively (P < 0.05). There was significant difference in the NRS scores among the four groups (P < 0.001). The NRS score of Group AB was significantly lower than that of Group P (P < 0.001), Group BP (P < 0.001) and Group AP (P = 0.001). At the same time, the NRS scores of Group BP (P < 0.001) and Group AP (P < 0.001) were significantly lower than those of Group P, but there was no significant difference between Group BP and Group AP (P = 1.000). The SBP, DBP, HR, the incidence of moderate to severe pain and the analgesia recovery ratio of Group AB were significantly lower than those of Group P (P < 0.05), while the SpO2 and the number of people who were very satisfied were significantly higher than those of Group P (P < 0.05). There was no significant difference in the incidence of adverse drug reactions among the four groups (P = 0.272). CONCLUSIONS: The combination or single use of pregabalin and tramadol/paracetamol can effectively relieve the acute pain after localization. Pregabalin combined with tramadol/paracetamol has the best analgesic effect and significantly reduces the hemodynamic fluctuations, with high safety and low incidence of adverse drug reactions, which has a certain clinical popularization and application value.

Anesthetic Management of One-Lung Ventilation in Patients With Tracheal Bronchus: A Narrative Review.

Tracheal bronchus is a rare congenital tracheal abnormality that generally refers to the right upper lobe bronchus of the lung that originates from the trachea. Tracheal bronchus is usually asymptomatic and is often accidentally detected by fiberoptic bronchoscopy or computed tomography for other conditions. Depending on the location of the tracheal bronchial opening and possible anatomical variations, the management of 1-lung ventilation in patients with tracheal bronchus is a significant challenge for anesthesiologists. To provide a reference for anesthesiologists to better manage anesthesia in such patients, we review the pathophysiology, definition, and Conacher classification of tracheal bronchus and then discuss the diagnosis of tracheal bronchus and management of 1-lung ventilation during anesthesia according to the Conacher classification.

Multimodal neuroimaging exploration of the mechanisms of sleep quality deterioration after SARS-CoV-2 Omicron infection.

BACKGROUND: To evaluate the neurological alterations induced by Omicron infection, to compare brain changes in chronic insomnia with those in exacerbated chronic insomnia in Omicron patients, and to examine individuals without insomnia alongside those with new-onset insomnia. METHODS: In this study, a total of 135 participants were recruited between January 11 and May 4, 2023, including 26 patients with chronic insomnia without exacerbation, 24 patients with chronic insomnia with exacerbation, 40 patients with no sleep disorder, and 30 patients with new-onset insomnia after infection with Omicron (a total of 120 participants with different sleep statuses after infection), as well as 15 healthy controls who were never infected with Omicron. Neuropsychiatric data, clinical symptoms, and multimodal magnetic resonance imaging data were collected. The gray matter thickness and T1, T2, proton density, and perivascular space values were analyzed. Associations between changes in multimodal magnetic resonance imaging findings and neuropsychiatric data were evaluated with correlation analyses. RESULTS: Compared with healthy controls, gray matter thickness changes were similar in the patients who have and do not have a history of chronic insomnia groups after infection, including an increase in cortical thickness near the parietal lobe and a reduction in cortical thickness in the frontal, occipital, and medial brain regions. Analyses showed a reduced gray matter thickness in patients with chronic insomnia compared with those with an aggravation of chronic insomnia post-Omicron infection, and a reduction was found in the right medial orbitofrontal region (mean [SD], 2.38 [0.17] vs. 2.67 [0.29] mm; P < 0.001). In the subgroups of Omicron patients experiencing sleep deterioration, patients with a history of chronic insomnia whose insomnia symptoms worsened after infection displayed heightened medial orbitofrontal cortical thickness and increased proton density values in various brain regions. Conversely, patients with good sleep quality who experienced a new onset of insomnia after infection exhibited reduced cortical thickness in pericalcarine regions and decreased proton density values. In new-onset insomnia patients post-Omicron infection, the thickness in the right pericalcarine was negatively correlated with the Self-rating Anxiety Scale (r = - 0.538, P = 0.002, PFDR = 0.004) and Self-rating Depression Scale (r = - 0.406, P = 0.026, PFDR = 0.026) scores. CONCLUSIONS: These findings help us understand the pathophysiological mechanisms involved when Omicron invades the nervous system and induces various forms of insomnia after infection. In the future, we will continue to pay attention to the dynamic changes in the brain related to insomnia caused by Omicron infection.

Self-supported porous wood carbon electrode with a MoC/carbon nanocage composite for application in a high-performance supercapacitor.

The rational design and synthesis of carbon nanocages with highly complex porous structures are continuously facing challenges in the development of high-performance supercapacitors (SCs). The electrochemical performance characteristics of electrodes rely on their compositions and fabrication methods. Here, we propose a universal and efficient approach for the in-situ synthesis of zeolitic imidazolate framework-8 (ZIF-8) on porous carbonized wood, where the selective utilization of hexacarbonyl molybdenum protects the structural integrity of the ZIF-8 precursor, preventing collapse during thermal treatment. The subsequent pyrolysis process leads to the formation of small-sized molybdenum carbide (MoC) which are embedded in carbon nanocages (CN). The composite electrode consists of MoC/CN embedded in a porous carbonized wood (PCW), and it shows area-specific capacity of 9.7F cm-2 and 9.4 F cm-2 at 5 mA cm-2 and 30 mA cm-2, respectively. Subsequently, the symmetric supercapacitor, with two MoC/CN@PCW electrodes exhibits a areal specific capacitance of 2.7 F cm-2 at 5 mA cm-2. Moreover, this supercapacitor maintains an capacitance retention rate of 98.5 % after 12,000 discharge cycles. The supercapacitor exhibits a power density of 6.5 mW cm-2, resulting in an energy density of 0.864 mWh cm-2. Therefore, the utilization of wood-based electrodes holds promise for energy storage systems.

Liquid-based cytology specimens for next-generation sequencing in lung adenocarcinoma: challenges and evaluation of targeted therapy.

BACKGROUND: To explore challenges of liquid-based cytology (LBC) specimens for next-generation sequencing (NGS) in lung adenocarcinoma and evaluate the efficacy of targeted therapy. METHODS: A retrospective analysis was conducted on the NGS test of 357 cases of advanced lung adenocarcinoma LBC specimens and compared with results of histological specimens to assess the consistency. The impact of tumor cellularity on NGS test results was evaluated. The utility of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) was collected. Clinical efficacy evaluation was performed and survival curve analysis was conducted using the Kaplan-Meier method. RESULTS: There were 275 TKI-naive and 82 TKI-treated specimens, the mutation rates of cancer-related genes detected in both groups were similar (86.2% vs. 86.6%). The EGFR mutation rate in the TKI treated group was higher than that in the TKI-naive group (69.5% > 54.9%, P = 0.019). There was no significant difference in the EGFR mutation frequency among different tumor cellularity in the TKI-naive group. However, in the TKI treated group, the frequency of EGFR sensitizing mutation and T790M resistance mutation in specimens with < 20% tumor cellularity was significantly lower than that in specimens with ≥ 20% tumor cellularity. Among 22 cases with matched histological specimens, 72.7% (16/22) of LBC specimens were completely consistent with results of histological specimens. Among 92 patients with EGFR-mutant lung adenocarcinoma treated with EGFR-TKIs in the two cohorts, 88 cases experienced progression, and the median progression-free survival (PFS) was 12.1 months. CONCLUSIONS: Cytological specimens are important sources for gene detection of advanced lung adenocarcinoma. When using LBC specimens for molecular testing, it is recommended to fully evaluate the tumor cellularity of the specimens.

The relationship between fear of cancer recurrence and posttraumatic growth: a meta-analysis.

Background: Theoretically, stress is positively correlated with posttraumatic growth (PTG). However, evidence for a correlation between fear of cancer recurrence (FCR), a cancer-specific stressor, and PTG is mixed. The present study aimed to systematically investigate the overall effect size between the two and to explore moderators that may influence this relationship. Methods: From the earliest available date to October 2023, a comprehensive search was conducted in seven databases. Correlation coefficients (r) were calculated using Stata software. Publication type, continent, trauma role, gender, FCR measurements, PTG measurements, sample size, age, and time since diagnosis were used to examine moderating effects. The National Heart, Lung, and Blood Institute's (NHLBI) assessment tool was used to evaluate study quality. Results: A total of 14 studies, involving 17 samples and 3,701 participants, were included. The studies found a small association between FCR and PTG (r = 0.161, 95% CI: 0.070-0.249, p < 0.01) and large heterogeneity (I2 = 85.5%). The strength of the association varied according to the publication type and FCR measurement. Conclusion: The current review suggests a small but significant positive correlation between FCR and PTG. Future studies would benefit from exploring additional moderators and the use of standardized, validated FCR measurement tools. Systematic review registration: PROSPERO, identifier CRD42023460407.

Ultrasensitive monitoring of PCB77 in environmental samples using a visible-driven photoelectrochemical sensing platform coupling with exonuclease I assisted in target recycling.

Due to the urgent need for detecting trace amounts of 3,3',4,4'-tetrachlorobiphenyl (PCB77) in the environment, we have developed an efficient and visible-driven photoelectrochemical (PEC) sensing platform based on carbon quantum dots (CQDs) modified titanium dioxide nanorods (TiO2 NRs), coupling with exonuclease I (Exo I) assisted in target recycling for significant signal amplification. CQDs/TiO2 NRs with high visible-light absorption ability and electron-hole separation efficiency is used as photoactive substrate for anchoring anti-PCB77 aptamer and its complementary DNA (cDNA). With the addition of PCB77, the specific interaction between PCB77 and its aptamer forces aptamer to separate from the electrode surface, resulting in an increase in photocurrent density. Adding Exo I in the test system, a self-catalytic target cycle was motivated, which significantly increased the PEC signal by more than twice, achieving signal amplification. The relationship between the photocurrent density changes and the concentrations of PCB77 are utilized to achieve quantitative detection of PCB77. The designed PEC sensing platform has good analytical performance with a detection limit as low as 0.33 pg L-1, high selectivity and stability. Moreover, the PEC sensor is successfully used to evaluate the content of PBC77 in the environment samples. The established sensing platform provides a simple and efficient method for detecting trace amounts of PCB77 in the environment.

High performance supercapacitors deploying cube-templated tracheid cavities of wood-derived carbon.

Wood-derived carbon, with its strong tracheid array structure, is an ideal material for use as a self-supporting electrode in supercapacitors. By leveraging the inherent through pore structure and surface affinity found in wood tracheids, we successfully engineered a highly spatially efficient cube-templated porous carbon framework inside carbonized wood tracheid cavities through precise control over precursor crystallization temperatures. This innovative cubic channel architecture effectively maximizes up to (79 ± 1)% of the cavity volume in wood-derived carbon while demonstrating exceptional hydrophilicity and high conductivity properties, facilitating the development of supercapacitors with enhanced areal/volumetric capacitances (2.65F cm-2/53.0F cm-3 at 5.0 mA cm-2) as well as superior areal/volumetric energy densities (0.37 mWh cm-2/7.36 mWh cm-3 at 2.5 mW cm-2). The fabrication of these cube-templated channels with high cube filling content is not only simple and precisely controllable, but also environmentally friendly. The proposed method eliminates the conventional acid-base treatment process for pore formation, facilitating the rapid development and practical implementation of thick electrodes with superior performance in supercapacitors. Moreover, it offers a universal research approach for the commercialization of wood-derived thick electrodes.

Association between social capital and utilization of essential public health services among elderly migrants: a multilevel logistic study based on the 2017 China migrant dynamic survey (CMDS).

BACKGROUND: As the number of elderly migrants in China continues to grow, it is necessary to pay closer attention to their health and health services. Some studies have confirmed that social capital plays a significant role in the utilization of health services. Therefore, an in-depth exploration of the relationship between social capital and the utilization of essential public health services (EPHS) by elderly migrants will not only contribute to improving their overall health but also facilitate a more balanced development of public health service system in China. METHODS: Based on the cross-sectional data from the 2017 China Migrants Dynamic Survey (CMDS), this study examined the impact of social capital on the utilization of EPHS among elderly migrants. We evaluated social capital at two distinct levels: the individual and the community, and considered two dimensions of social capital: structural social capital (SSC) and cognitive social capital (CSC). The study aimed to delve into the impact of these forms of social capital on the utilization of EPHS among elderly migrants, and whether the migration range moderates this impact by multilevel logistic regression analysis. RESULTS: A total of 5,728 migrant elderly individuals were selected. The health records establishment rate and health education acceptance rate were approximately 33.0% and 58.6%, respectively. Social capital influenceed the utilization of EPHS among elderly migrants. Specifically, individual-level SSC and CSC have impacts on both the establishment of health records (OR = 1.598, 95%CI 1.366-1.869; OR = 1.705, 95%CI 1.433-2.028) and the acceptance of health education (OR = 1.345, 95%CI 1.154-1.567; OR = 2.297, 95%CI 1.906-2.768) among elderly migrants, while community-level SSC only affected the acceptance of health education (OR = 3.838, 95%CI 1.328-11.097). There were significant differences in individual-level SSC, health records, and health education among different migration range subgroups among elderly migrants. Migration range moderated the effect of social capital on the utilization of EPHS, crossing provinces could weaken the relationship between SSC and health education. CONCLUSIONS: Social capital is associated with a higher utilization rate of EPHS among elderly migrants. It is necessary to encourage them to actively participate in social activities, strengthen public services and infrastructure construction in the area, and improve their sense of belonging and identity.

From tissue lesions to neurotoxicity: The devastating effects of small-sized nanoplastics on red drum Sciaenops ocellatus.

Nanoplastic pollution typically exhibits more biotoxicity to marine organisms than microplastic pollution. Limited research exists on the toxic effects of small-sized nanoplastics on marine fish, especially regarding their post-exposure resilience. In this study, red drum (Sciaenops ocellatus) were exposed to small-sized polystyrene nanoplastics (30 nm, PS-NPs) for 7 days for the exposure experiments, followed by 14 days of recovery experiments. Histologically, hepatic lipid droplets and branchial epithelial liftings were the primary lesions induced by PS-NPs during both exposure and recovery periods. The inhibition of total superoxide dismutase activity and the accumulation of malondialdehyde content throughout the exposure and recovery periods. Transcriptional and metabolic regulation revealed that PS-NPs induced lipid metabolism disorders and DNA damage during the initial 1-2 days of exposure periods, followed by immune responses and neurotoxicity in the later stages (4-7 days). During the early recovery stages (2-7 days), lipid metabolism and cell cycle were activated, while in the later recovery stage (14 days), the emphasis shifted to lipid metabolism and energy metabolism. Persistent histological lesions, changes in antioxidant capacity, and fluctuations in gene and metabolite expression were observed even after 14 days of recovery periods, highlighting the severe biotoxicity of small-sized PS-NPs to marine fish. In summary, small-sized PS-NPs have severe biotoxicity, causing tissue lesions, oxidative damage, lipid metabolism disorders, DNA damage, immune responses, and neurotoxicity in red drum. This study offers valuable insights into the toxic effects and resilience of small-sized nanoplastics on marine fish.

ADCY4 promotes brain metastasis in small cell lung cancer and is associated with energy metabolism.

Brain metastasis (BMs) in small cell lung cancer (SCLC) has a very poor prognosis. This study combined WGCNA with the mfuzz algorithm to identify potential biomarkers in the peripheral blood of patients with BMs. By comparing the significantly differentially expressed genes present in BMs samples, we identified ADCY4 as a target for further study. Expression of ADCY4 was used to cluster mfuzz expression pattern, and 28 hub genes for functional enrichment. PPI network analysis were obtained by comparing with differentially expressed genes in BMs. GABRE, NFE4 and LMOD2 are highly expressed in patients with BMs and have a good diagnostic effect. Immunoinfiltration analysis showed that SCLC patients with BMs may be associated with memory B cells, Tregs, NK cell activation, macrophage M0 and dendritic cell activation. prophytic was used to investigate the ADCY4-mediated anti-tumor drug response. In conclusion, ADCY4 can be used as a promising candidate biomarker for predicting BMs, molecular and immune features in SCLC. PCR showed that ADCY4 expression was increased in NCI-H209 and NCI-H526 SCLC cell lines. In vitro experiments confirmed that the expression of ADCY4 was significantly decreased after anti-PD1 antibody treatment, while the expression of energy metabolism factors were significantly different. This study reveals a potential mechanism by which ADCY4 mediates poor prognosis through energy metabolism -related pathways in SCLC.

Consistency Analysis of Programmed Death Ligand 1 Expression in Non-Small Cell Lung Cancer Between Pleural Effusion and Matched Primary Lung Cancer Tissues by Immunohistochemical Double Staining.

In clinical practice, programmed death ligand 1 (PD-L1) detection is prone to nonspecific staining due to the complex cellular composition of pleural effusion smears. In this study, diaminobenzidine (DAB) and 3-amino-9-ethylcarbazole (AEC) immunohistochemistry double staining was performed to investigate PD-L1 expression in tumor cells from malignant pleural effusion (MPE). MPE was considered as a metastasis in non-small cell lung cancer patients; thus, the heterogeneity between metastatic and primary lung cancer was revealed as well. Ninety paired specimens of MPE cell blocks and matched primary lung cancer tissues from non-small cell lung cancer patients were subjected to PD-L1 and thyroid transcription factor-1(TTF-1)/p63 immunohistochemistry double staining. Two experienced pathologists independently evaluated PD-L1 expression using 3 cutoffs (1%, 10%, and 50%). PD-L1 expression in MPE was strongly correlated with that in matched primary lung cancer tissues (R = 0.813; P < .001). Using a 4-tier scale (cutoffs: 1%, 10%, and 50%), the concordance was 71.1% (Cohen's κ = .534). Using a 2-tier scale, the concordance was 75.6% (1%, Cohen's κ = 0.53), 78.9% (10%, Cohen's κ = 0.574), and 95.6% (50%, Cohen's κ = 0.754). The rates of PD-L1 positivity in MPE (56.7%) were higher than that in lung tissues (32.2%). All 27 discordant cases had higher scores in MPE. The double-staining method provided superior identification of PD-L1-positive tumor cells on a background with nonspecific staining. In conclusion, PD-L1 expression was moderately concordant between metastatic MPE cell blocks and matched primary lung carcinoma tissues, with variability related to tumor heterogeneity. MPE should be considered to detect PD-L1 when histological specimens are unattainable, especially when PD-L1 expression is >50%. PD-L1 positivity rates were higher in MPE. Double staining can improve PD-L1 detection by reducing false-negative/positive results.

Autophagy-mediated degradation of integumentary tapetum is critical for embryo pattern formation.

Autophagy modulates the degradation and recycling of intracellular materials and contributes to male gametophyte development and male fertility in plants. However, whether autophagy participates in seed development remains largely unknown. Here, we demonstrate that autophagy is crucial for timely programmed cell death (PCD) in the integumentary tapetum, the counterpart of anther tapetum, influencing embryo pattern formation and seed viability. Inhibition of autophagy resulted in delayed PCD of the integumentary tapetum and defects in embryo patterning. Cell-type-specific restoration of autophagic activities revealed that the integumentary tapetum plays a non-autonomous role in embryo patterning. Furthermore, high-throughput, comprehensive lipidomic analyzes uncovered an unexpected seed-developmental-stage-dependent role of autophagy in seed lipid metabolism: it contributes to triacylglycerol degradation before fertilization and to triacylglycerol biosynthesis after fertilization. This study highlights the critical role of autophagy in regulating timely integumentary tapetum PCD and reveals its significance in seed lipid metabolism and viability.

Immunosenescence and immunotherapy in older NSCLC patients.

Nonsmall cell lung cancer (NSCLC) predominantly affects the elderly since its incidence and mortality rates skyrocket beyond the age of 65. The landscape of NSCLC treatment has been revolutionized by immune checkpoint inhibitors (ICIs), which have emerged after a long and mostly inactive period of conventional treatment protocols. However, there is limited data on the exact effects of these chemicals on older patients, whose care can be complicated by a variety of conditions. This highlights the need to understand the efficacy of emerging cancer medicines in older patients. In this study, we will review the data of ICIs from clinical trials that were relevant to older people with NSCLC and poor performance status. We will also discuss the role of immunosenescence in immunotherapy and biomarkers in predicting the efficacy of ICIs in patients with advanced NSCLC.