Community Composition and Functional Characterization of Microorganisms in Surface Sediment of the New Britain Trench.

The deep-sea harbors abundant prokaryotic biomass is a major site of organic carbon remineralization and long-term carbon burial in the ocean. Deep-sea trenches are the deepest part of the ocean, and their special geological and morphological features promoting the accumulation of organic matter and active organic carbon turnover. Despite the expanding reports about the organic matter inputs, limited information is known regarding microbial processes in deep-sea trenches. In this study, we investigated the species composition and metabolic potential in surface sediment of the New Britain Trench (NBT), using a metagenomic approach. The predominant microbial taxa in NBT sediment include Proteobacteria, Acidobacteria, Planctomycetes, Actinobacteria and Chloroflexota. The microbial communities showed highly diverse metabolic potentials. Particularly, genes encoding enzymes for degradation of aromatic compounds, as well as those encoding haloalkane dehalogenase and haloacetate dehalogenase were annotated in the NBT surface sediment, which indicate the potential of microorganisms to degrade different types of refractory organic matter. The functional genes encoding enzymes for dissimilatory nitrate reduction, denitrification, and nitrification were also represented in the NBT metagenome. Overall, the microbial communities show high diversity of heterotrophic lineages and metabolic features, supporting their potential contributions in organic carbon metabolism. Meanwhile, Nitrosopumilus, a dominant genus in the surface sediment of the NBT, is a typical ammonia-oxidizing archaea (AOA), with autotrophic CO2 fixation pathways including the 3-hydroxypropionate/4-hydroxybutylate (3HP/4HB) cycle, the reductive TCA (rTCA) cycle. The results demonstrate that autotrophic metabolic processes also play an important role in the surface sediment, by providing newly synthesized organic matter.

Mechanism of action of the Banxia-Xiakucao herb pair in sleep deprivation: New comprehensive evidence from network pharmacology, transcriptomics and molecular biology experiments.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herb pairs are the most basic and compressed examples of Chinese herbal combinations and can be used to effectively explain the fundamental concepts of traditional Chinese medicine prescriptions. These pairings have gained significant interest due to their subtle therapeutic benefits, minimal side effects, and efficacy in treating complicated chronic conditions. The Banxia-Xiakucao Chinese herb pair (BXHP) consists of Pinellia ternata (Thunb.) Breit. (Banxia) and Prunella vulgaris L. (Xiakucao). This formula was documented in The Medical Classic of the Yellow Emperor approximately 2000 years ago，and clinical research has demonstrated that BXHP effectively treats insomnia. AIM OF THE STUDY: This study aimed to evaluate the efficacy and therapeutic mechanism of the BXHP through a comprehensive strategy involving network pharmacology, molecular docking, transcriptomics, and molecular biology experimental validation. MATERIALS AND METHODS: The composition of BXHP was characterized using the UPLC-Q-TOF-MS. The active compounds were screened to find drug-likeness compounds by analyzing the ADME data. To predict the molecular mechanism of BXHP in sleep deprivation (SD) by network pharmacology and molecular docking. We established a rat model of SD and the in vivo efficacy of BXHP was verified through the pentobarbital sodium righting reflex test, behavioral assays, enzyme-linked immunosorbent assay, transmission electron microscopy, HE staining, and Nissl staining, and the underlying molecular mechanism of BXHP in SD was revealed through transcriptomic and bioinformatic analyses in conjunction with quantitative real-time PCR, Western blot, and immunofluorescence staining. RESULTS: In the present study, we showed for the first time that BXHP reduced sleep latency, prolongs sleep duration, and improves anxiety; lowered serum CORT, IL6, TNF-α and MDA levels; decreased hypothalamic Glu levels; and elevated hypothalamic GABA and 5-HT levels in SD rats. We found 16 active compounds that acted on 583 targets, 145 of which are related to SD. By modularly dissecting the PPI network, we discovered three critical targets, Akt1, CREB1, and PRKACA, all of which play important roles in the effects of BXHP on SD. Molecular docking resulted in the identification of 16 active compounds that strongly bind to key targets. The results of GO and KEGG enrichment analyses of network pharmacology and transcriptomics focused on both the regulation of circadian rhythm and the cAMP signaling pathway, which strongly demonstrated that BXHP affects SD via the cAMP-PKA-CREB-Circadian rhythm pathway. Molecular biology experiments verified this hypothesis. Following BXHP administration, PKA and CREB phosphorylation levels were elevated in SD rats, the cAMP-PKA-CREB signaling pathway was activated, the expression levels of the biological clock genes CLOCK, p-BMAL1/BMAL1, and PER3 were increased, and the rhythmicity of the biological clock was improved. CONCLUSIONS: The active compounds in BXHP can activate the cAMP-PKA-CREB-Circadian rhythm pathway, improve the rhythmicity of the biological clock, promote sleep and ameliorate anxiety, which suggests that BXHP improves SD through a multicomponent, multitarget, multipathway mechanism. This study is important for the development of herbal medicines and clinical therapies for improving sleep deprivation.

Discrepancies between self-reported medication in adherence and indirect measurement adherence among patients undergoing antiretroviral therapy: a systematic review.

BACKGROUND: Given the critical importance of medication adherence in HIV/AIDS treatment, this study aims to compare medication adherence measured by self-report (SR) and indirect measurement among antiretroviral therapy (ART) patients, exploring the differences of adherence results measured by different tools. METHODS: We systematically searched PubMed, Embase, and the Cochrane Library to identify all relevant literature published up to November 22, 2023, without language restrictions, reporting adherence to ART measured by both SR and indirect measurement methods, while also analyzing individual and group adherence separately. Discrepancies between SR and indirect measurement results were assessed using the Mann-Whitney U test or Wilcoxon signed-rank test, with correlations evaluated using the Pearson correlation coefficient. Following one-to-one comparisons, meta-epidemiological one-step analysis was conducted, and network meta-analysis techniques were applied to compare results obtained through specific adherence assessment tools reported in the identified articles. RESULTS: The analysis encompassed 65 original studies involving 13,667 HIV/AIDS patients, leading to 112 one-to-one comparisons between SR and indirect measurement tools. Statistically significant differences were observed between SR and indirect measurement tools regarding both individual and group adherence (P < 0.05), with Pearson correlation coefficients of 0.843 for individual adherence and 0.684 for group adherence. During meta-epidemiological one-step analysis, SR-measured adherence was determined to be 3.94% (95% CI: -4.48-13.44%) higher for individual adherence and 16.14% (95% CI: 0.81-18.84%) higher for group adherence compared to indirectly measured results. Subgroup analysis indicated that factors such as the year of reporting and geographic region appeared to influence the discrepancies between SR and indirect measurements. Furthermore, network meta-analysis revealed that for both individual and group adherence, the results obtained from most SR and indirect measurement tools were higher than those from electronic monitoring devices, with some demonstrating statistical significance (P < 0.05). CONCLUSIONS: The findings underscored the complexity of accurately measuring medication adherence among ART patients. Significant variability was observed across studies, with self-report methods showing a significant tendency towards overestimation. Year of reporting, geographic region, and adherence measurement tools appeared to influence the differences between SR and indirect measurements. Future research should focus on developing and validating integrated adherence measurements that can combine SR data with indirect measures to achieve a more comprehensive understanding of adherence behaviors.

Modifying the Substrate-Dependent Pd/Fe2O3 Catalyst-Support Synergism with ZnO Atomic Layer Deposition.

Low-loading Pd supported on Fe2O3 nanoparticles was synthesized. A common nanocatalyst system with previously reported synergistic enhancement of reactivity that is attributed to the electronic interactions between Pd and the Fe2O3 support. Fe2O3-selective precoalescence overcoating with ZnO atomic layer deposition (ALD), using Zn(CH2CH3)2 and H2O as precursors, dampens competitive hydrogenation reactivity at Fe2O3-based sites. The result is enhanced efficiency at the low-loading but high reactivity Pd sites. While this increases catalyst efficiency toward most aqueous redox reactions tested, it suppresses reactivity toward polyaromatic core substrates. X-ray photoelectron spectroscopy (XPS) and ultraviolet photoelectron spectroscopy (UPS) show minimal electronic impacts for the ZnO overcoat on the Pd particles, implying a predominantly physical site blocking effect as the reason for the modified reactivity. This serves as a proof-of-concept of not only stabilizing supported nanocatalysts but also altering reactivity with ultrathin ALD overcoats. The results point to a facile ALD route for selective enhancement of reactivity for low-loading Pd-based supported nanocatalysts.

HT-2 toxin impairs porcine oocyte in vitro maturation through disruption of endomembrane system.

HT-2 toxin is a type of mycotoxin which is shown to affect gastric and intestinal lesions, hematopoietic and immunosuppressive effects, anorexia, lethargy, nausea. Recently, emerging evidences indicate that HT-2 also disturbs the reproductive system. In this study, we investigated the impact of HT-2 toxin exposure on the organelles of porcine oocytes. Our results found that the abnormal distribution of endoplasmic reticulum increased after HT-2 treatment, with the perturbation of ribosome protein RPS3 and GRP78 expression; Golgi apparatus showed diffused localization pattern and GM130 localization was also impaired, thereby affecting the Rab10-based vesicular transport; Due to the impairment of ribosomes, ER, and Golgi apparatus, the protein supply to lysosomes was hindered, resulting in lysosomal damage, which further disrupted the LC3-based autophagy. Moreover, the results indicated that the function and distribution of mitochondria were also affected by HT-2 toxin, showing with fragments of mitochondria, decreased TMRE and ATP level. Taken together, our study suggested that HT-2 toxin exposure induces damage to the organelles for endomembrane system, which further inhibited the meiotic maturation of porcine oocytes.

AC-ModNet: Molecular Reverse Design Network Based on Attribute Classification.

Deep generative models are becoming a tool of choice for exploring the molecular space. One important application area of deep generative models is the reverse design of drug compounds for given attributes (solubility, ease of synthesis, etc.). Although there are many generative models, these models cannot generate specific intervals of attributes. This paper proposes a AC-ModNet model that effectively combines VAE with AC-GAN to generate molecular structures in specific attribute intervals. The AC-ModNet is trained and evaluated using the open 250K ZINC dataset. In comparison with related models, our method performs best in the FCD and Frag model evaluation indicators. Moreover, we prove the AC-ModNet created molecules have potential application value in drug design by comparing and analyzing them with medical records in the PubChem database. The results of this paper will provide a new method for machine learning drug reverse design.

Rapid identification of early infections in febrile patients after CD19 target CAR-T cell therapy for B-cell malignancies.

BACKGROUND: CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy stands out as a revolutionary intervention, exhibiting remarkable remission rates in patients with refractory/relapsed (R/R) B-cell malignancies. However, the potential side effects of therapy, particularly cytokine release syndrome (CRS) and infections, pose significant challenges due to their overlapping clinical features. Promptly distinguishing between CRS and infection post CD19 target CAR-T cell infusion (CTI) remains a clinical dilemma. Our study aimed to analyze the incidence of infections and identify key indicators for early infection detection in febrile patients within 30 days post-CTI for B-cell malignancies. METHODS: In this retrospective cohort study, a cohort of 104 consecutive patients with R/R B-cell malignancies who underwent CAR-T therapy was reviewed. Clinical data including age, gender, CRS, ICANS, treatment history, infection incidence, and treatment responses were collected. Serum biomarkers procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) levels were analyzed using chemiluminescent assays. Statistical analyses employed Pearson's Chi-square test, t-test, Mann-Whitney U-test, Kaplan-Meier survival analysis, Cox proportional hazards regression model, Spearman rank correlation, and receiver operating characteristic (ROC) curve analysis to evaluate diagnostic accuracy and develop predictive models through multivariate logistic regression. RESULTS: In this study, 38 patients (36.5%) experienced infections (30 bacterial, 5 fungal, and 3 viral) within the first 30 days of CAR T-cell infusion. In general, bacterial, fungal, and viral infections were detected at a median of 7, 8, and 9 days, respectively, after CAR T-cell infusion. Prior allogeneic hematopoietic cell transplantation (HCT) was an independent risk factor for infection (Hazard Ratio [HR]: 4.432 [1.262-15.565], P = 0.020). Furthermore, CRS was an independent risk factor for both infection ((HR: 2.903 [1.577-5.345], P < 0.001) and severe infection (9.040 [2.256-36.232], P < 0.001). Serum PCT, IL-6, and CRP were valuable in early infection prediction post-CAR-T therapy, particularly PCT with the highest area under the ROC curve (AUC) of 0.897. A diagnostic model incorporating PCT and CRP demonstrated an AUC of 0.903 with sensitivity and specificity above 83%. For severe infections, a model including CRS severity and PCT showed an exceptional AUC of 0.991 with perfect sensitivity and high specificity. Based on the aforementioned analysis, we proposed a workflow for the rapid identification of early infection during CAR-T cell therapy. CONCLUSIONS: CRS and prior allogeneic HCT are independent infection risk factors post-CTI in febrile B-cell malignancy patients. Our identification of novel models using PCT and CRP for predicting infection, and PCT and CRS for predicting severe infection, offers potential to guide therapeutic decisions and enhance the efficacy of CAR-T cell therapy in the future.

Intratumoral Microbiota as a Target for Advanced Cancer Therapeutics.

In recent years, advancements in microbial sequencing technology have sparked an increasing interest in the bacteria residing within solid tumors and its distribution and functions in various tumors. Intratumoral bacteria critically modulate tumor oncogenesis and development through DNA damage induction, chronic inflammation, epigenetic alterations, and metabolic and immune regulation, while also influencing cancer treatment efficacy by affecting drug metabolism. In response to these discoveries, a variety of anti-cancer therapies targeting these microorganisms have emerged. These approaches encompass oncolytic therapy utilizing tumor-associated bacteria, the design of biomaterials based on intratumoral bacteria, the use of intratumoral bacterial components for drug delivery systems, and comprehensive strategies aimed at the eradication of tumor-promoting bacteria. Herein, this review article summarizes the distribution patterns of bacteria in different solid tumors, examines their impact on tumors, and evaluates current therapeutic strategies centered on tumor-associated bacteria. Furthermore, the challenges and prospects for developing drugs that target these bacterial communities are also explored, promising new directions for cancer treatment.

Hyponatremia Is Associated with Mortality in Acute Pancreatitis Patients.

BACKGROUND: Disorders of serum sodium are common among general patients and are associated with poor outcomes. The prognostic value of serum sodium disorders in patients with acute pancreatitis (AP) has not been studied. We conducted this retrospective study to explore the association between serum sodium levels and the outcomes of patients with AP. MATERIALS AND METHODS: Patients with AP from the Medical Information Mart for Intensive Care III (MIMIC-III) were screened for this study. The laboratory variables, including serum sodium levels, were obtained by analyzing the first blood sample on the first day after admission. Univariate logistic regression was performed to discover potential factors for mortality of AP. The unadjusted and adjusted association between serum sodium level and mortality of AP was shown by the restricted cubic spline (RCS). The categorical cutoff for the detrimental effect of serum sodium level on the prognosis of AP was also confirmed by stepwise logistic regression after adjusting for con-founding effects of significant factors in the univariate logistic regression. RESULTS: A total of 869 patients with AP in the MIMIC-III were included with a mortality of 13.1%. Unadjusted logistic regression showed that age (p < 0.001), simplified acute physiological score (SAPS) (p < 0.001), systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), hemoglobin (p = 0.040), serum creatinine (p = 0.046), and serum phosphorus (p < 0.001) were significantly associated with the mortality of AP. The RCS showed that the serum sodium level was negatively and linearly associated with mortality of AP after adjusting for confounding effects of significant factors in the univariate logistic regression. Serum sodium < 133 mmol/L, which indicated hyponatremia, was significantly correlated with a higher mortality risk than serum sodium ≥ 133 mmol/L (p = 0.013). CONCLUSIONS: Hyponatremia is widely developed among patients with AP and correlates with a higher mortality risk of AP. Physicians should pay more attention to managing patients with AP with hyponatremia.

Harnessing Bacterial Membrane Components for Tumor Vaccines: Strategies and Perspectives.

Tumor vaccines stand at the vanguard of tumor immunotherapy, demonstrating significant potential and promise in recent years. While tumor vaccines have achieved breakthroughs in the treatment of cancer, they still encounter numerous challenges, including improving the immunogenicity of vaccines and expanding the scope of vaccine application. As natural immune activators, bacterial components offer inherent advantages in tumor vaccines. Bacterial membrane components, with their safer profile, easy extraction, purification, and engineering, along with their diverse array of immune components, activate the immune system and improve tumor vaccine efficacy. This review systematically summarizes the mechanism of action and therapeutic effects of bacterial membranes and its derivatives (including bacterial membrane vesicles and hybrid membrane biomaterials) in tumor vaccines. Subsequently, the authors delve into the preparation and advantages of tumor vaccines based on bacterial membranes and hybrid membrane biomaterials. Following this, the immune effects of tumor vaccines based on bacterial outer membrane vesicles are elucidated, and their mechanisms are explained. Moreover, their advantages in tumor combination therapy are analyzed. Last, the challenges and trends in this field are discussed. This comprehensive analysis aims to offer a more informed reference and scientific foundation for the design and implementation of bacterial membrane-based tumor vaccines.

Translation, cross-cultural adaptation, and measurement properties of the Traditional Chinese version of the Fear of Falling Avoidance Behavior Questionnaire in Taiwanese community-dwelling adults.

PURPOSE: This study aimed to translate the Fear of Falling Avoidance Behavior Questionnaire (FFABQ) into Traditional Chinese (FFABQ-TC) and to evaluate the psychometric properties of FFABQ-TC in Taiwanese adults. METHODS: We translated and culturally adapted the FFABQ into Traditional Chinese, ensuring linguistic accuracy and cultural relevance. A total of 230 Taiwanese community-dwelling adults participated in the study. Test-retest reliability was assessed in 30 participants, while 200 participants were included in the validity analysis. Known-groups validity was investigated by comparing the FFABQ-TC scores between fallers and non-fallers. Convergent validity was examined by correlating FFABQ-TC scores with Activities-specific Balance Confidence Scale (ABC), Geriatric Fear of Falling Measure (GFFM), and Timed-Up-and-Go (TUG) test. RESULTS: The FFABQ-TC demonstrated excellent test-retest reliability (Intraclass Correlation Coefficient = 0.884) and excellent internal consistency (Cronbach's alpha = 0.930). Known-groups analysis revealed that FFABQ-TC significantly differentiated between fallers and non-fallers. Convergent validity was examined and showed significant correlations of FFABQ-TC with the ABC, the GFFM, and TUG. CONCLUSION: The psychometric properties of FFABQ-TC was established in Taiwanese adults for assessing FOF-related avoidance behaviors. The translated and adapted FFABQ-TC is a reliable and valid clinical tool for evaluating fall risk in this population.

The current evidence supports the reliability and validity of the Traditional Chinese version of the Fear of Falling Avoidance Behavior Questionnaire (FFABQ-TC) in Taiwanese community-dwelling adults.FFABQ-TC is recommended as a reliable measurement to determine fall risk in clinical and research settings.

Clinical application of voriconazole in pediatric patients: a systematic review.

The purpose of this study was to review the literature on the clinical use of voriconazole (VRC) in pediatric patients. MEDLINE, Embase, PubMed, Web of Science, and Cochrane Library were searched from January 1, 2000, to August 15, 2023 for relevant clinical studies on VRC use in pediatric patients. Data were collected based on inclusion and exclusion criteria, and a systematic review was performed on recent research related to the use of VRC in pediatric patients. This systematic review included a total of 35 observational studies among which there were 16 studies investigating factors influencing VRC plasma trough concentrations (Ctrough) in pediatric patients, 14 studies exploring VRC maintenance doses required to achieve target range of Ctrough, and 11 studies focusing on population pharmacokinetic (PPK) research of VRC in pediatric patients. Our study found that the Ctrough of VRC were influenced by both genetic and non-genetic factors. The optimal dosing of VRC was correlated with age in pediatric patients, and younger children usually required higher VRC doses to achieve target Ctrough compared to older children. Establishing a PPK model for VRC can assist in achieving more precise individualized dosing in children.

Endogenous stem cell mobilization and localized immunosuppression synergistically ameliorate DSS-induced Colitis in mice.

BACKGROUND: Stem cell therapy is a promising alternative for inflammatory diseases and tissue injury treatment. Exogenous delivery of mesenchymal stem cells is associated with instant blood-mediated inflammatory reactions, mechanical stress during administration, and replicative senescence or change in phenotype during long-term culture in vitro. In this study, we aimed to mobilize endogenous hematopoietic stem cells (HSCs) using AMD-3100 and provide local immune suppression using FK506, an immunosuppressive drug, for the treatment of inflammatory bowel diseases. METHODS: Reactive oxygen species (ROS)-responsive FK506-loaded thioketal microspheres were prepared by emulsification solvent-evaporation method. Thioketal vehicle based FK506 microspheres and AMD3100 were co-administered into male C57BL6/J mice with dextran sulfate sodium (DSS) induced colitis. The effect of FK506-loaded thioketal microspheres in colitis mice were evaluated using disease severity index, myeloperoxidase activity, histology, flow cytometry, and gene expression by qRT-PCR. RESULTS: The delivery of AMD-3100 enhanced mobilization of HSCs from the bone marrow into the inflamed colon of mice. Furthermore, targeted oral delivery of FK506 in an inflamed colon inhibited the immune activation in the colon. In the DSS-induced colitis mouse model, the combination of AMD-3100 and FK506-loaded thioketal microspheres ameliorated the disease, decreased immune cell infiltration and activation, and improved body weight, colon length, and epithelial healing process. CONCLUSION: This study shows that the significant increase in the percentage of mobilized hematopoietic stem cells in the combination therapy of AMD and oral FK506 microspheres may contribute to a synergistic therapeutic effect. Thus, low-dose local delivery of FK506 combined with AMD3100 could be a promising alternative treatment for inflammatory bowel diseases.

Lightweight cotton diseases real-time detection model for resource-constrained devices in natural environments.

Cotton, a vital textile raw material, is intricately linked to people's livelihoods. Throughout the cotton cultivation process, various diseases threaten cotton crops, significantly impacting both cotton quality and yield. Deep learning has emerged as a crucial tool for detecting these diseases. However, deep learning models with high accuracy often come with redundant parameters, making them challenging to deploy on resource-constrained devices. Existing detection models struggle to strike the right balance between accuracy and speed, limiting their utility in this context. This study introduces the CDDLite-YOLO model, an innovation based on the YOLOv8 model, designed for detecting cotton diseases in natural field conditions. The C2f-Faster module replaces the Bottleneck structure in the C2f module within the backbone network, using partial convolution. The neck network adopts Slim-neck structure by replacing the C2f module with the GSConv and VoVGSCSP modules, based on GSConv. In the head, we introduce the MPDIoU loss function, addressing limitations in existing loss functions. Additionally, we designed the PCDetect detection head, integrating the PCD module and replacing some CBS modules with PCDetect. Our experimental results demonstrate the effectiveness of the CDDLite-YOLO model, achieving a remarkable mean average precision (mAP) of 90.6%. With a mere 1.8M parameters, 3.6G FLOPS, and a rapid detection speed of 222.22 FPS, it outperforms other models, showcasing its superiority. It successfully strikes a harmonious balance between detection speed, accuracy, and model size, positioning it as a promising candidate for deployment on an embedded GPU chip without sacrificing performance. Our model serves as a pivotal technical advancement, facilitating timely cotton disease detection and providing valuable insights for the design of detection models for agricultural inspection robots and other resource-constrained agricultural devices.

Mitochondrial endogenous substance transport-inspired nanomaterials for mitochondria-targeted gene delivery.

Mitochondrial genome (mtDNA) independent of nuclear gene is a set of double-stranded circular DNA that encodes 13 proteins, 2 ribosomal RNAs and 22 mitochondrial transfer RNAs, all of which play vital roles in functions as well as behaviors of mitochondria. Mutations in mtDNA result in various mitochondrial disorders without available cures. However, the manipulation of mtDNA via the mitochondria-targeted gene delivery faces formidable barriers, particularly owing to the mitochondrial double membrane. Given the fact that there are various transport channels on the mitochondrial membrane used to transfer a variety of endogenous substances to maintain the normal functions of mitochondria, mitochondrial endogenous substance transport-inspired nanomaterials have been proposed for mitochondria-targeted gene delivery. In this review, we summarize mitochondria-targeted gene delivery systems based on different mitochondrial endogenous substance transport pathways. These are categorized into mitochondrial steroid hormones import pathways-inspired nanomaterials, protein import pathways-inspired nanomaterials and other mitochondria-targeted gene delivery nanomaterials. We also review the applications and challenges involved in current mitochondrial gene editing systems. This review delves into the approaches of mitochondria-targeted gene delivery, providing details on the design of mitochondria-targeted delivery systems and the limitations regarding the various technologies. Despite the progress in this field is currently slow, the ongoing exploration of mitochondrial endogenous substance transport and mitochondrial biological phenomena may act as a crucial breakthrough in the targeted delivery of gene into mitochondria and even the manipulation of mtDNA.

Benzo[a]pyrene exposure disrupts the organelle distribution and function of mouse oocytes.

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon compound that is generated during combustion processes, and is present in various substances such as foods, tobacco smoke, and burning emissions. BaP is extensively acknowledged as a highly carcinogenic substance to induce multiple forms of cancer, such as lung cancer, skin cancer, and stomach cancer. Recently it is shown to adversely affect the reproductive system. Nevertheless, the potential toxicity of BaP on oocyte quality remains unclear. In this study, we established a BaP exposure model via mouse oral gavage and found that BaP exposure resulted in a notable decrease in the ovarian weight, number of GV oocytes in ovarian, and oocyte maturation competence. BaP exposure caused ribosomal dysfunction, characterized by a decrease in the expression of RPS3 and HPG in oocytes. BaP exposure also caused abnormal distribution of the endoplasmic reticulum (ER) and induced ER stress, as indicated by increased expression of GRP78. Besides, the Golgi apparatus exhibited an abnormal localization pattern, which was confirmed by the GM130 localization. Disruption of vesicle transport processes was observed by the abnormal expression and localization of Rab10. Additionally, an enhanced lysosome and LC3 fluorescence intensity indicated the occurrence of protein degradation in oocytes. In summary, our results suggested that BaP exposure disrupted the distribution and functioning of organelles, consequently affecting the developmental competence of mouse oocytes.

Association of waist circumference and BMI with premature death in young and middle-aged population.

Introduction: Premature death is a global health indicator, significantly impacted by obesity, especially in young and middle-aged population. Both body mass index (BMI) and waist circumference (WC) assess obesity, with WC specifically indicating central obesity and showing a stronger relationship with mortality. However, despite known associations between BMI and premature death, as well as the well-recognized correlation between WC and adverse health outcomes, the specific relationship between WC and premature death remains unclear. Therefore, focusing on young and middle-aged individuals, this study aimed to reliably estimate independent and combined associations between WC, BMI and premature death, thereby providing causal evidence to support strategies for obesity management. Methods: This study involved 49,217 subjects aged 18-50 years in the United States from 1999 to 2018 National Health and Nutrition Examination Survey (NHANES). Independent and combined associations between WC and BMI with premature death across sex and age stratum were examined by Cox regression. Survey weighting and inverse probability weighting (IPW) were further considered to control selection and confounding bias. Robustness assessment has been conducted on both NHANES and China Health and Retirement Longitudinal Study (CHARLS) data. Results: A linear and positive relationship between WC and all-cause premature death was found in both males and females, with adjusted HRs of 1.019 (95%CI = 1.004-1.034) and 1.065 (95%CI = 1.039-1.091), respectively. Nonlinear relationships were found with respect to BMI and all-cause premature death. For females aged 36-50 with a BMI below 28.6 kg/m2, the risk of premature death decreased as BMI increased, indicated by adjusted HRs of 0.856 (95%CI = 0.790-0.927). Joint analysis showed among people living with obesity, a larger WC increased premature death risk (HR = 1.924, 95%CI = 1.444-2.564). Discussion: WC and BMI exhibited prominent associations with premature death in young and middle-aged population. Maintaining an appropriate WC and BMI bears significant implications for preventing premature death.

The Value of Perioperative Immunotherapy for Non-Small Cell Lung Cancer: A Pool- and Meta-Analysis.

Purpose: This study aimed to analyze the efficacy and safety of neoadjuvant and adjuvant immunotherapies for non-small cell lung cancer (NSCLC). Methods: Electronic literature searches were conducted in PubMed, OVID, Web of SCI, Embase, Cochrane Library, and the Chinese National Knowledge Infrastructure databases. The deadline for literature update and retrieval is February 16, 2024. Studies presented at meetings were also screened. Randomized controlled trials (RCTs) and single-arm trials were included, and the data were extracted according to the inclusion and exclusion criteria. Data analysis was performed using Stata (16.0) software. Results: A total of 5850 patients in 11 RCTs and 6 single-arm trial studies involving neoadjuvant and/or adjuvant immune checkpoint inhibitor (ICI)-based therapies were included. Regarding neoadjuvant therapy, the overall complication rate after surgery reached 35% (95% CI, 0.21-0.49). Higher rates of pathological complete response (OR = 7.83; 95% CI, 5.95-10.31; P < .001) and major pathological response (OR = 5.13; 95% CI, 3.56-7.40; P < .001) were found in the resectable NSCLC patients who received neoadjuvant therapy with ICIs combined with chemotherapy compared with patients treated with chemotherapy alone. Of note, compared with chemotherapy, neoadjuvant ICIs combined with chemotherapy significantly improved the overall survival (OS) (HR = 0.65; 95% CI, 0.52-0.82; P < .001) and event-free survival (EFS) (HR = 0.59; 95% CI, 0.52-0.67; P < .001) in patients with resectable NSCLC. Regarding adjuvant therapy, a lower risk of disease progression or death (HR = 0.78; 95% CI, 0.69-0.90; P < .001) was found in the adjuvant ICI group compared with the adjuvant chemotherapy-alone group. In terms of safety, perioperative immunotherapy combined with chemotherapy did not increase toxicity compared with chemotherapy alone. Conclusion: In patients with resectable NSCLC, perioperative immunotherapy was safe and efficacious. Perioperative immunotherapy combined with chemotherapy improved the pathologic response and EFS/DFS/OS over chemotherapy alone without increasing toxicity.

Unraveling the Molecular Weight Dependence of High Magnetic Field to Manipulate the Semiconducting Polymer Molecular Orientation.

The magnetic alignment of molecules, which exploits the anisotropy of diamagnetic susceptibility, provides a clean and versatile approach to the structural manipulation of semiconducting polymers. Here, the magnetic-alignment dynamics of two molecular-weight (MW) batches of a diketopyrrolopyrrole (DPP)-based copolymer (PDVT-8) were investigated. Microstructural characterizations revealed that the magnetically aligned, high-MW (Mn = 53.7 kDa) PDVT-8 film exhibited a higher degree of backbone chain alignment and film crystallinity compared with the low-MW (Mn = 17.6 kDa) PDVT-8 film grown via the same magnetic alignment method. We found that as the MW increases, the degree of preaggregation of the polymer molecules in solution significantly increases and the aggregation mode changes from H-aggregation to J-aggregation through a cooperative assembly mechanism. These events improved the responsiveness of high-MW polymer molecules to magnetic fields. Field-effect transistors based on the magnetic aligned high-MW PDVT-8 films exhibited a 6.8-fold increase in hole mobility compared to the spin-coated films, along with a mobility anisotropy ratio of 12.6. This work establishes a significant correlation among chain aggregation behavior in solution, polymer film microstructures, magnetic responsiveness, and carrier transport performance in donor-acceptor polymer systems.

The correlation between drivers' road familiarity and glance behavior using real vehicle experimental data and mathematical models.

OBJECTIVE: Road familiarity is an important factor affecting drivers' visual features. Analyzing the quantitative correlation between drivers' road familiarity and visual features in complex environment is of great help to improve driving safety. However, there are few relevant studies. This paper takes urban plane intersection as the environmental object to explore the correlation between drivers' glance behavior and road familiarity, and conducts research on the quantitative evaluation model of road familiarity based on this correlation. METHOD: First, a real vehicle experiment was carried out to record the eye movement data of 24 drivers with different road familiarity. The driver's visual field plane was divided into 10 areas of interest (AOIs) based on the driver's perspective. Three measures, including average glance duration, number of glances, and fixation transition probabilities between AOIs at urban plane intersections, were extracted. Finally, based on the experimental results, the driver road familiarity evaluation model was constructed using the factor analysis method. RESULTS: There are significant differences between unfamiliar and familiar drivers regarding the average glance duration toward the forward (FW) area, the left window (LW) area, the left rearview mirror (LVM) area and the left forward (LF) area, the number of glances toward the other (OT) area, and the fixation transition probabilities of LW→RF (right forward), LF→LF, LF→FW, FW→LW, FW→FW, FW→RVM (right rearview mirror). The comprehensive evaluation results show that the accuracy rate of the driver road familiarity evaluation model reached 83%. CONCLUSIONS: This paper revealed that there is a strong correlation between drivers' road familiarity and drivers' glance behavior. Based on this correlation, we can include road familiarity as a part of drivers' working status and establish a high accuracy evaluation model of driver road familiarity. The conclusion of this paper can provide some reference for the humanized design and improvement of advanced driving assistance system, which is of great significance for reducing the driving workload of drivers and improving the driving safety.