Black soldier fly larvae bioconversion and subsequent composting promote larval frass quality during pig and chicken manure transformation process.

This research systematically assessed the changes in carbon, nitrogen and microbial profiling during pig and chicken manure transformation by black soldier fly larvae (BSFL) and subsequent composting process. BSFL had higher conversion efficiency for chicken manure. The pH, phosphorus and potassium contents in fresh BSFL frass increased than raw manure, but conductivity, total-/nitrate-/ammonium-nitrogen decreased. After BSFL conversion, pig manure had a larger nitrogen loss (25 %) while chicken manure had a larger carbon loss (32 %). During subsequent composting, the indicator changes (e.g. humus, ammonium nitrogen) in frass composts basically remained stable after 20-30 days. Compared to natural composts, frass composts had higher humification degree, cellulase activities, and more cellulose-degrading bacteria. Subsequent composting further reduced potential pathogens (reduced by 98.9 %-99.7 % than raw manure), and elevated the aromaticity and humification of frass. The findings gave an insight into the maturation management of manure-sourced insect frass.

Diagnosis and treatment of the Ehlers-Danlos syndromes in China: synopsis of the first guidelines.

BACKGROUND: The Ehlers-Danlos syndromes (EDS) are a group of rare hereditary connective tissue disorders. EDS is clinically and genetically heterogeneous and usually involves multiple systems. There are 14 subtypes of EDS with hallmark features including joint hypermobility, skin hyperextensibility, and tissue fragility. The clinical manifestations and their severity differ among the subtypes, encompassing recurrent joint dislocations, scoliosis, arterial aneurysm and dissection, and organ rupture. Challenges in diagnosis and management arise from the complexity of the disease, which is further complicated by its rarity. The development of clinical guidelines and implementation of coordinated multi-disciplinary team (MDT) approaches have emerged as global priorities. MAIN BODY: Chinese Multi-Disciplinary Working Group on the Ehlers-Danlos Syndromes was therefore established. Healthcare professionals were recruited from 25 top hospitals across China. The experts are specialized in 24 fields, including genetics, vascular surgery, dermatology, and orthopedics, as well as nursing care, rehabilitation, psychology, and nutrition. Based on GRADE methodology, the Guidelines were written by the Group supervised by methodologists, following a systemic review of all 4453 articles in PubMed published before August 9, 2023, using the search term "Ehlers Danlos". A coordinated MDT approach for the diagnosis and management of EDS is highly recommended by the Group, along with 29 specific recommendations addressing key clinical questions. In addition to the treatment plan, the Guidelines also emphasize integrating support from nursing care, rehabilitation, psychology, and nutrition. This integration not only facilitates recovery in hospital settings, but most importantly, the transition from an illness-defined life to a more "normalized" life. CONCLUSION: The first guidelines on EDS will shorten the diagnostic odyssey and solve the unmet medical needs of the patients. This article is a synopsis of the full guidelines.

Rare variant association analyses reveal the significant contribution of carbohydrate metabolic disturbance in severe adolescent idiopathic scoliosis.

BACKGROUND: Adolescent idiopathic scoliosis (AIS), the predominant genetic-influenced scoliosis, results in spinal deformities without vertebral malformations. However, the molecular aetiology of AIS remains unclear. METHODS: Using genome/exome sequencing, we studied 368 patients with severe AIS (Cobb angle >40°) and 3794 controls from a Han Chinese cohort. We performed gene-based and pathway-based weighted rare variant association tests to assess the mutational burden of genes and established biological pathways. Differential expression analysis of muscle tissues from 14 patients with AIS and 15 controls was served for validation. RESULTS: SLC16A8, a lactate transporter linked to retinal glucose metabolism, was identified as a novel severe AIS-associated gene (p=3.08E-06, false discovery rate=0.009). Most AIS cases with deleterious SLC16A8 variants demonstrated early onset high myopia preceding scoliosis. Pathway-based burden test also revealed a significant enrichment in multiple carbohydrate metabolism pathways, especially galactose metabolism. Patients with deleterious variants in these genes demonstrated a significantly larger spinal curve. Genes related to catabolic processes and nutrient response showed divergent expression between AIS cases and controls, reinforcing our genomic findings. CONCLUSION: This study uncovers the pivotal role of genetic variants in carbohydrate metabolism in the development of AIS, unveiling new insights into its aetiology and potential treatment.

An antioxidant hydrogel dressing with wound pH indication function prepared based on silanized bacterial nanocellulose crosslinked with beet red pigment extract.

Maintaining wound moisture and monitoring of infection are crucial aspects of chronic wound treatment. The development of a pH-sensitive functional hydrogel dressing is an effective approach to monitor, protect, and facilitate wound healing. In this study, beet red pigment extract (BRPE) served as a native and efficient pH indicator by being grafted into silane-modified bacterial nanocellulose (BNC) to prepare a pH-sensitive wound hydrogel dressing (S-g-BNC/BRPE). FTIR confirmed the successful grafting of BRPE into the BNC matrix. The S-g-BNC/BRPE showed superior mechanical properties (0.25 MPa), swelling rate (1251 % on average), and hydrophilic properties (contact angle 21.83°). The composite exhibited a notable color change as the pH changed between 4.0 and 9.0. It appeared purple-red when the pH ranged from 4.0 to 6.0, and appeared light pink at pH 7.0 and 7.4, and appeared ginger-yellow at pH 8.0 and 9.0. Subsequently, the antioxidant activity and cytotoxicity of the composite was evaluated, its DPPH·, ABTS+, ·OH scavenging rates were 32.33 %, 19.31 %, and 30.06 %, respectively, and the cytotoxicity test clearly demonstrated the safety of the dressing. The antioxidant hydrogel dressing, fabricated with a cost-effective and easy method, not only showed excellent biocompatibility and dressing performance but could also indicated the wound state based on pH changes.

Characteristics of inclusions in chang 7 member and shale oil accumulation stages in Zhijing-Ansai area, Ordos Basin.

In order to further clarify the shale oil accumulation period of the Chang 7 member of the Mesozoic Triassic Yanchang Formation in the Zhijing-Ansai area of the central Ordos Basin, Using fluid inclusion petrography analysis, microscopic temperature measurement, salinity analysis and fluorescence spectrum analysis methods, combined with the burial history-thermal history recovery in the area, the oil and gas accumulation period of the Chang 7 member of the Yanchang Formation in the Zhijing-Ansai area was comprehensively analyzed. Sixteen shale oil reservoir samples of the Mesozoic Triassic Yanchang Formation in seven typical wells in the study area were selected.The results show that the fluid inclusions in the Chang 7 member of Yanchang Formation can be divided into two stages. The first stage inclusions mainly develop liquid hydrocarbon inclusions and a large number of associated brine inclusions, which are mainly beaded in fracture-filled quartz and fracture-filled calcite. The fluorescence color is blue and blue-green, and the homogenization temperature of the associated brine inclusions is between 90-110°C. The second stage inclusions are mainly gas-liquid two-phase hydrocarbon inclusions, gas inclusions and asphalt inclusions. Most of them are distributed in the fracture-filled quartz, and the temperature of the associated brine inclusions is between 120-130°C. Fluid inclusions in Chang 7 member of the Yanchang Formation can be divided into two stages. The CO2 inclusions and high temperature inclusions in the Chang 7 member of the Yanchang Formation are mainly derived from deep volcanic activity in the crust.

Toxic mechanisms of nanoplastics exposure at environmental concentrations on juvenile red swamp crayfish (Procambarus clarkii): from multiple perspectives.

Nanoplastics pollution has emerged as a global issue due to its widespread potential toxicity. This study delved in to toxic effects of nanoplastics on juvenile P. clarkii and molecular mechanisms from perspectives of growth, biochemical, histopathological analysis and transcriptome level for the first time. The findings of this study indicated that nanoplastics of different concentrations have varying influence mechanisms on juvenile P. clarkii. Nanoplastics have inhibitory effects on growth of juvenile P. clarkii, can induce oxidative stress. The biochemical analysis and transcriptome results indicated that 10mg/L nanoplastics can activate the antioxidant defense system and non-specific immune system in juvenile P. clarkii, and affect energy metabolism and oxidative phosphorylation. While 20mg/L and 40mg/L have a destructive influence on the immune function in juvenile P. clarkii, leading to lipid peroxidation and oxidative damage, and induce apoptosis, can affect ion transport and osmotic pressure regulation. The findings of this study can offer foundational data for delving further into impacts of nanoplastics on crustaceans and toxicity mechanism.

Genetic and phenotypic profiling of single living circulating tumor cells from patients with microfluidics.

Accurate prediction of the efficacy of immunotherapy for cancer patients through the characterization of both genetic and phenotypic heterogeneity in individual patient cells holds great promise in informing targeted treatments, and ultimately in improving care pathways and clinical outcomes. Here, we describe the nanoplatform for interrogating living cell host-gene and (micro-)environment (NICHE) relationships, that integrates micro- and nanofluidics to enable highly efficient capture of circulating tumor cells (CTCs) from blood samples. The platform uses a unique nanopore-enhanced electrodelivery system that efficiently and rapidly integrates stable multichannel fluorescence probes into living CTCs for in situ quantification of target gene expression, while on-chip coculturing of CTCs with immune cells allows for the real-time correlative quantification of their phenotypic heterogeneities in response to immune checkpoint inhibitors (ICI). The NICHE microfluidic device provides a unique ability to perform both gene expression and phenotypic analysis on the same single cells in situ, allowing us to generate a predictive index for screening patients who could benefit from ICI. This index, which simultaneously integrates the heterogeneity of single cellular responses for both gene expression and phenotype, was validated by clinically tracing 80 non-small cell lung cancer patients, demonstrating significantly higher AUC (area under the curve) (0.906) than current clinical reference for immunotherapy prediction.

Transcriptome-Wide N6-Methyladenosine (m6A) Methylation Analyses in a Compatible Wheat-Puccinia striiformis f. sp. tritici Interaction.

N6-methyladenosine (m6A) is a prevalent internal modification in eukaryotic mRNA, tRNA, miRNA, and long non-coding RNA. It is also known for its role in plant responses to biotic and abiotic stresses. However, a comprehensive m6A transcriptome-wide map for Puccinia striiformis f. sp. tritici (Pst) infections in wheat (Triticum aestivum) is currently unavailable. Our study is the first to profile m6A modifications in wheat infected with a virulent Pst race. Analysis of RNA-seq and MeRIP-seq data revealed that the majority of differentially expressed genes are up-regulated and hyper-methylated. Some of these genes are enriched in the plant-pathogen interaction pathway. Notably, genes related to photosynthesis showed significant down-regulation and hypo-methylation, suggesting a potential mechanism facilitating successful Pst invasion by impairing photosynthetic function. The crucial genes, epitomizing the core molecular constituents that fortify plants against pathogenic assaults, were detected with varying expression and methylation levels, together with a newly identified methylation motif. Additionally, m6A regulator genes were also influenced by m6A modification, and their expression patterns varied at different time points of post-inoculation, with lower expression at early stages of infection. This study provides insights into the role of m6A modification regulation in wheat's response to Pst infection, establishing a foundation for understanding the potential function of m6A RNA methylation in plant resistance or susceptibility to pathogens.

Circ_005077 accelerates myocardial lipotoxicity induced by high-fat diet via CyPA/p47PHOX mediated ferroptosis.

The long-term high-fat diet (HFD) can cause myocardial lipotoxicity, which is characterized pathologically by myocardial hypertrophy, fibrosis, and remodeling and clinically by cardiac dysfunction and heart failure in patients with obesity and diabetes. Circular RNAs (circRNAs), a novel class of noncoding RNA characterized by a ring formation through covalent bonds, play a critical role in various cardiovascular diseases. However, few studies have been conducted to investigate the role and mechanism of circRNA in myocardial lipotoxicity. Here, we found that circ_005077, formed by exon 2-4 of Crmp1, was significantly upregulated in the myocardium of an HFD-fed rat. Furthermore, we identified circ_005077 as a novel ferroptosis-related regulator that plays a role in palmitic acid (PA) and HFD-induced myocardial lipotoxicity in vitro and in vivo. Mechanically, circ_005077 interacted with Cyclophilin A (CyPA) and inhibited its degradation via the ubiquitination proteasome system (UBS), thus promoting the interaction between CyPA and p47phox to enhance the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase responsible for ROS generation, subsequently inducing ferroptosis. Therefore, our results provide new insights into the mechanisms of myocardial lipotoxicity, potentially leading to the identification of a novel therapeutic target for the treatment of myocardial lipotoxicity in the future.

Ultrasmall iron oxide nanoparticles with MRgFUS for enhanced magnetic resonance imaging of orthotopic glioblastoma.

Ultrasmall iron oxide nanoparticles (USIO NPs) are expected to become the next generation T1 contrast agents; however, their diagnostic and therapeutic potential for primary brain tumors (such as glioblastoma multiforme, GBM) is yet to be explored. At present, the main challenge is the effective hindering of biological barriers, including the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB). Herein, we aimed to investigate whether the USIO NPs, in combination with MR-guided focused ultrasound (MRgFUS), could intensify MR imaging of GBM. In this study, we presented zwitterionic USIO NPs for enhanced MR imaging of both xenografted and orthotopic GBM mouse models. We first synthesized citric-stabilized USIO NPs with a size of 3.19 ± 0.76 nm, modified with ethylenediamine, and decorated with 1,3-propanesultone (1,3-PS) to form USIO NPs-1,3-PS. The obtained USIO NPs-1,3-PS exhibited good cytocompatibility and cellular uptake efficiency. MRgFUS, in combination with microbubbles, provided a non-invasive and safe technique for BBB opening, which, in turn, promoted the delivery of USIO NPs-1,3-PS in orthotopic GBM. This developed USIO NP nanoplatform may improve the precision imaging of solid tumors and therapeutic efficacy in the central nervous system.

Model informed drug development: HSK21542 PBPK model supporting dose decisions in specific populations.

HKS21542, a highly selective activator of peripheral kappa opioid receptor agonists, plays a critical role in antinociception and itch inhibition during clinical development. Due to its indication population and elimination characteristics, it is imperative to evaluate the potential HSK21542 systemic exposure in individuals with renal impairment, hepatic impairment, the elderly, and the geriatric population. Here, a physiologically-based pharmacokinetic (PBPK) model for HSK21542 was developed based on in vitro metabolism and transport characteristics and in vivo elimination mechanism. Meanwhile, the potential systemic exposure of HSK21542 in specific populations was evaluated. The predicted results indicated increased systemic exposure in patients with renal impairment, hepatic impairment and in the elderly. Compared to the healthy volunteers aged 20-60 years, the AUC0-24h increased by 52 %-71 % in population with moderate to severe renal impairment, by 46 %-77 % in those with mild to severe hepatic impairment, and by 45 %-85 % in the elderly population aged 65-95-years. Conversely, the pediatric population demonstrated a potential decrease in systemic exposure, ranging from 20 % to 37 % in patients aged 0-17 years due to the physiological characteristics. Combined with the predicted results and the exposure-response relationship observed for HSK21542 and its analog (CR845), dosage regimens were designed for the target population with renal and hepatic impairment, supporting the successfully conducted trials (CTR20201702 and CTR20211940). Moreover, the observed exposure of HSK21542 in the elderly closely matched the predicted results within the same age group. Additionally, based on the predicted results, potential reductions in systemic exposure in pediatric patients should be carefully considered to avoid potential treatment failure in future clinical trials.

Win-win or lose-lose: Children prefer the form of equality.

In middle childhood, children's sense of fairness further develops, they are willing to pay a cost to maintain equality. Win-win and lose-lose are two forms of equality. Win-win equality refers to both parties maximizing benefits, while lose-lose equality means both parties incurring the maximum loss. Win-win equality allows third party upholding fairness to gain more reputational benefits without the violator being punished, embodying the principle of "benefiting oneself without harming others". On the other hand, lose-lose equality is a more deterrent form of fairness with the violator getting punished, and the third-party might experience a situation of "effort without appreciation." However, the specific form of equality which school-aged children prefer still requires further exploration. Therefore, adopting the dictator game paradigm of third-party punishment, we design two experiments to investigate the fairness preference of first to fourth-grade children when acting as a third party and to clarify patterns of age-related changes. Study 1 (N = 111) explored children's preferred form of fairness under advantageous inequity conditions. Study 2 (N = 122) further examined children's fairness preferences in disadvantageous inequity situations. The findings suggest that when confronted with inequitable distributions, whether rooted in disadvantageous or advantageous inequity, children display a notable tendency to utilize third-party punishment to achieve an equal allocation. Meanwhile, this tendency strengthens as they progress in grade levels. Notably, children consistently manifest a preference for win-win equality, highlighting their inclination towards mutually beneficial outcomes.

Host proteins interact with viral elements and affect the life cycle of highly pathogenic avian influenza A virus H7N9.

Host-virus interactions can significantly impact the viral life cycle and pathogenesis; however, our understanding of the specific host factors involved in highly pathogenic avian influenza A virus H7N9 (HPAI H7N9) infection is currently restricted. Herein, we designed and synthesized 65 small interfering RNAs targeting host genes potentially associated with various aspects of RNA virus life cycles. Afterward, HPAI H7N9 viruses were isolated and RNA interference was used to screen for host factors likely to be involved in the life cycle of HPAI H7N9. Moreover, the research entailed assessing the associations between host proteins and HPAI H7N9 proteins. Twelve key host proteins were identified: Annexin A (ANXA)2, ANXA5, adaptor related protein complex 2 subunit sigma 1 (AP2S1), adaptor related protein complex 3 subunit sigma 1 (AP3S1), ATP synthase F1 subunit alpha (ATP5A1), COPI coat complex subunit alpha (COP)A, COPG1, heat shock protein family A (Hsp70) member 1A (HSPA)1A, HSPA8, heat shock protein 90 alpha family class A member 1 (HSP90AA1), RAB11B, and RAB18. Co-immunoprecipitation revealed intricate interactions between viral proteins (hemagglutinin, matrix 1 protein, neuraminidase, nucleoprotein, polymerase basic 1, and polymerase basic 2) and these host proteins, presumably playing a crucial role in modulating the life cycle of HPAI H7N9. Notably, ANXA5, AP2S1, AP3S1, ATP5A1, HSP90A1, and RAB18, were identified as novel interactors with HPAI H7N9 proteins rather than other influenza A viruses (IAVs). These findings underscore the significance of host-viral protein interactions in shaping the dynamics of HPAI H7N9 infection, while highlighting subtle variations compared with other IAVs. Deeper understanding of these interactions holds promise to advance disease treatment and prevention strategies.

[GmAGB1 plays a positive regulatory role in soybean defense responses].

Heterotrimeric GTP-binding protein (G-proteins) complex, which consists of Gα, Gß and Gγ subunits, plays critical roles in defense signaling. Arabidopsis genome contains only a single Gß-encoding gene, AGB1. Loss function of AGB1 in Arabidopsis results in enhanced susceptibility to a wide range of pathogens. However, the function of soybean AGB1 in immunity has not been previously interrogated. Bioinformatic analysis indicated that there are four GmAGB1 homologous genes in soybean genome, sharing homology of 86%-97%. To overcome the functional redundancy of these GmAGB1 homologs, virus-induced gene silencing (VIGS) mediated by the bean pod mottle virus (BPMV) was used to silence these four genes simultaneously. As expected, these four GmAGB1 homologous genes were indeed silenced by a single BPMV-VIGS vector carrying a conserved fragments among these four genes. A dwarfed phenotype was observed in GmAGB1s-silenced soybean plants, suggesting that GmAGB1s play a crucial role in growth and development. Disease resistance analysis indicated that silencing GmAGB1s significantly compromised the resistance of soybean plants against Xanthomonas campestris pv. glycinea (Xag). This reduced resistance was correlated with the decreased accumulation of pathogen-induced reactive oxygen species (ROS) and the reduced activation of GmMPK3 in response to flg22, a conserved N-terminal peptide of flagellin protein. These results indicate that GmAGB1 functions as a positive regulator in disease resistance and GmAGB1 is indispensable for the ROS production and GmMPK3 activation induced by pathogen infection. Yeast two hybrid assay showed that GmAGB1 interacted with GmAGG1, suggesting that an evolutionary conserved heterotrimeric G protein complex similarly functions in soybean.

Effectiveness of Virtual Reality-Based Interventions for Upper Limb Rehabilitation in Breast Cancer Patients: Systematic Review and Meta-Analysis.

Purpose: To investigate the effectiveness of virtual reality (VR)-based interventions for functional rehabilitation of the upper limb in breast cancer patients through a systematic review and meta-analysis. Methods: The PubMed, Cochrane, Web of Science, CINAHL, Scopus, CNKI, Wanfang, and VIP databases were systematically searched for relevant literature published from the establishment of the database to June 2023. Differences in the effectiveness of VR-based interventions and other intervention therapies were compared using random effects model meta-analysis and standard deviation (SMD). Results: Seven eligible articles were identified and included in the meta-analysis. The combined analysis found that VR-based interventions had a positive impact on patients' upper limb mobility in terms of flexion (SMD = 1.33, 95% confidence interval; CI [0.48-2.19], P = 0.002), abduction (SMD = 1.22, 95% CI [0.58-1.86], P = 0.0002), and external rotation (SMD = 0.94, 95% CI [0.48-1.40], P < 0.0001). In addition, VR-based interventions could significantly improve the postoperative pain of patients with breast cancer. However, in grip strength (SMD = 0.43, 95% CI [-3.05 to 3.92], P = 0.81), shoulder muscle strength in flexion strength (SMD = 0.05, 95% CI [-2.07 to 2.18], P = 0.96), abduction strength (SMD = -0.10, 95% CI [-1.32 to 1.12], P = 0.88), external rotation strength (SMD = 0.46, 95% CI [-1.96 to 2.88], P = 0.71), and lymphedema, VR was as effective as other intervention treatments. A subgroup analysis showed that patients younger than 55 years had more benefit with VR-based rehabilitation than with other interventions and showed improvements with the intervention within 2 weeks. The intervention effect of using auxiliary equipment such as robotic arms is better than VR exercise based solely on games. Conclusion: The results of meta-analysis show that the intervention measures based on VR have positive effects on the improvement of upper limb mobility and pain relief in breast cancer patients. However, considering the low quality of evidence and small sample size, more clinical studies should be conducted to improve the credibility of the results.

Patient-derived tumor-like cell clusters for personalized chemo- and immunotherapies in non-small cell lung cancer.

Many patient-derived tumor models have emerged recently. However, their potential to guide personalized drug selection remains unclear. Here, we report patient-derived tumor-like cell clusters (PTCs) for non-small cell lung cancer (NSCLC), capable of conducting 100-5,000 drug tests within 10 days. We have established 283 PTC models with an 81% success rate. PTCs contain primary tumor epithelium self-assembled with endogenous stromal and immune cells and show a high degree of similarity to the original tumors in phenotypic and genotypic features. Utilizing standardized culture and drug-response assessment protocols, PTC drug-testing assays reveal 89% overall consistency in prospectively predicting clinical outcomes, with 98.1% accuracy distinguishing complete/partial response from progressive disease. Notably, PTCs enable accurate prediction of clinical outcomes for patients undergoing anti-PD1 therapy by combining cell viability and IFN-γ value assessments. These findings suggest that PTCs could serve as a valuable preclinical model for personalized medicine and basic research in NSCLC.

Core planar cell polarity genes VANGL1 and VANGL2 in predisposition to congenital vertebral malformations.

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear. Here, we investigated the role of Vangl1 and Vangl2 in vertebral development and found that their deletion causes vertebral anomalies resembling human CVMs. Analysis of exome sequencing data from multiethnic CS patients revealed a number of rare and deleterious variants in VANGL1 and VANGL2, many of which exhibited loss-of-function and dominant-negative effects. Zebrafish models confirmed the pathogenicity of these variants. Furthermore, we found that Vangl1 knock-in (p.R258H) mice exhibited vertebral malformations in a Vangl gene dose- and environment-dependent manner. Our findings highlight critical roles for PCP signaling in vertebral development and predisposition to CVMs in CS patients, providing insights into the molecular mechanisms underlying this disorder.

Deciphering and predicting changes in antibiotic resistance genes during pig manure aerobic composting via machine learning model.

Livestock manure is one of the most important pools of antibiotic resistance genes (ARGs) in the environment. Aerobic composting can effectively reduce the spread of antibiotic resistance risk in livestock manure. Understanding the effect of aerobic composting process parameters on manure-sourced ARGs is important to control their spreading risk. In this study, the effects of process parameters on ARGs during aerobic composting of pig manure were explored through data mining based on 191 valid data collected from literature. Machine learning (ML) models (XGBoost and Random Forest) were utilized to predict the rate of ARGs changes during pig manure composting. The model evaluation index of the XGBoost model (R2 = 0.651) was higher than that of the Random Forest (R2 = 0.490), indicating that XGBoost had better prediction performance. Feature importance was further calculated for the XGBoost model, and the XGBoost black box model was interpreted by Shapley additive explanations analysis. Results indicated that the influencing factors on the ARGs variation in pig manure were sequentially divided into thermophilic period, total composting period, composting real time, and thermophilic stage average temperature. The findings gave an insight into the application of ML models to predict and decipher the ARG changes during manure composting and provided suggestions for better composting manipulation and optimization of process parameters.

Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer.

Lung cancer, ranking second globally in both incidence and high mortality among common malignant tumors, presents a significant challenge with frequent occurrences of drug resistance despite the continuous emergence of novel therapeutic agents. This exacerbates disease progression, tumor recurrence, and ultimately leads to poor prognosis. Beyond acquired resistance due to genetic mutations, mounting evidence suggests a critical role of epigenetic mechanisms in this process. Numerous studies have indicated abnormal expression of Histone Methyltransferases (HMTs) in lung cancer, with the abnormal activation of certain HMTs closely linked to drug resistance. HMTs mediate drug tolerance in lung cancer through pathways involving alterations in cellular metabolism, upregulation of cancer stem cell-related genes, promotion of epithelial-mesenchymal transition, and enhanced migratory capabilities. The use of HMT inhibitors also opens new avenues for lung cancer treatment, and targeting HMTs may contribute to reversing drug resistance. This comprehensive review delves into the pivotal roles and molecular mechanisms of HMTs in drug resistance in lung cancer, offering a fresh perspective on therapeutic strategies. By thoroughly examining treatment approaches, it provides new insights into understanding drug resistance in lung cancer, supporting personalized treatment, fostering drug development, and propelling lung cancer therapy into novel territories.

Beneficial implications of adjuvant chemotherapy for stage IB lung adenocarcinoma exhibiting elevated SUVmax in FDG-PET/CT: a retrospective study from a single center.

Background: Controversy surrounds the efficacy of adjuvant chemotherapy (ACT) in the treatment of stage I lung adenocarcinoma (LUAD). The objective of this study was to examine the impact of the maximum standardized uptake value (SUVmax) as measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) on the efficacy of ACT in patients diagnosed with stage I LUAD. Methods: We scrutinized the medical records of 928 consecutive patients who underwent complete surgical resection for pathological stage I LUAD at our institution. The ideal cut-off value for primary tumor SUVmax in terms of disease-free survival (DFS) and overall survival (OS) was determined using the X-tile software. The Kaplan-Meier method and Cox regression analysis were used for survival analysis. Results: Based on the SUVmax algorithm, the ideal cutoff values were determined to be 4.9 for DFS and 5.0 for OS. We selected 5.0 as the threshold because OS is the more widely accepted predictive endpoint. In a multivariate Cox regression analysis, SUVmax ≥ 5.0, problematic IB stage, and sublobectomy were identified as independent risk factors for poor DFS and OS. It is noteworthy that patients who were administered ACT had significantly longer DFS and OS than what was observed in the subgroup of patients with pathological stage IB LUAD and SUVmax ≥ 5.0 (p < 0.035 and p ≤ 0.046, respectively). However, there was no observed survival advantage for patients in stages IA or IB who had an SUVmax < 5.0. Conclusion: The preoperative SUVmax of tumors served as an indicator of the impact of ACT in the context of completely resected pathological stage I LUAD. Notably, patients within the Stage IB category exhibiting elevated SUVmax levels emerged as a subgroup experiencing substantial benefits from postoperative ACT.