Identification of a Mnlrig-1 involved in testis reproductive immunity in the oriental river prawn Macrobrachium nipponense.

The testis evolves a highly organized testicular microenvironment to support spermatogenesis. However, the knowledge about it is limited in crustacean. In this study, we identified a member of immunoglobulin superfamily (IgSF) from Macrobrachium nipponense testis and explored its roles as a potential pattern recognition receptor (PRR) involved in reproductive immunity. Based on the domains it contains and homology analysis result, we designate it as leucine-rich repeats and immunoglobulin-like domains protein-1 (MnLrig-1). The Mnlrig-1 comprises a 3288 bp open reading frame (ORF) encoding a 1095 amino acid protein. MnLrig-1 is consisted of one signaling peptide; one LRR_NT domain; eight LRR domains; five LRR_TYP domains; one LRR_CT domain; three IGc2 regions; one transmembrane region, and C-terminal cytoplasmic tail, sharing similar domains with orthologs in other crustacean species. MnLrig-1 is widely expressed in various tissues of M. nipponense. Mnlrig-1 is significantly induced by LPS, PGN, Aeromonas hydrophila, and Vibrio alginolyticus challenge in the testis at 3 h and maintained a high level from 3 h to 24 h. Additionally, two recombinant immunoglobulin domains of MnLrig-1 are obtained, while only one domain shows direct binding affinity towards LPS, PGN, Escherichia coli, A. hydrophila, Staphylococcus aureus, and Bacillus subtilis in vitro. Moreover, silencing Mnlrig-1 results in a significant upregulation of three anti-lipopolysaccharide factors (ALFs) in the testis. These results reveal the potential role of MnLrig-1 as a PRR involved in the testis reproductive immunity in M. nipponense. The insights gained from this study will expand our understanding of immune system in crustacean and may have implications for aquaculture and disease management in crustaceans.

Ecological risk threshold for chromium in Chinese soils and its prediction models.

The derivation of chromium (Cr) ecological risk thresholds in soils remains limited, despite their importance as measurement standards and indicators for enacting soil protection policies. In this study, toxicity of Cr in soil to different species was tested based on Log-Logistic dose-effect relationship. On this basis, combined with Cr toxicity measurement data in literature, the ecological risk threshold HC5 for protecting 95% species safety in soils with different properties was obtained by fitting species sensitivity distribution curve (SSD). This research collected various Cr toxicological data from Chinese cropland soils, based on 31 different endpoints covering soil fauna, functional indicators of microorganisms, terrestrial plants, etc., sourced from both our laboratory and existing literature. We applied the SSD method to estimate the hazardous concentration of Cr for HC5 and ultimately established a predictive model according to HC5 and different soil properties. As a result, the EC10 (an effective concentration of Cr resulting in 10% suppression of terminal biological activity) based on 7 different soils and 4 endpoints ranged from 16.8 to 148.0 mg kg-1, and the hormesis of Cr induction reached up to 109%. Overall, the toxicity (EC10) to microorganisms was much lower, while it was higher for graminoids. All the toxicity data were corrected through an aging factor with up to 540 days of equilibration before fitting the SSD curves. After that, a prediction model considering HC5 values and soil properties was established as LogHC5 = 3.003LogpH +0.651LogOC +0.013LogCEC - 0.476. The model was well-verified in field experiments, as the actual and predicted values fell within a 2-fold error range. This approach offers a rigorous scientific foundation for determining the Cr ecological risk threshold and could be important for the conservation of ecological species in soils.

VUV Activated Fe(VI) by Promoting the Generation of Intermediate Valent Iron and Hydroxyl Radicals.

In this study, vacuum ultraviolet (VUV) was first proposed to activate ferrate (Fe(VI)) for degrading micropollutants (e.g., carbamazepine (CBZ)). Results indicated that VUV/Fe(VI) could significantly facilitate the CBZ degradation, and the removal efficiencies of VUV/Fe(VI) were 30.9-83.4% higher than those of Fe(VI) at pH = 7.0-9.0. Correspondingly, the degradation rate constants of VUV/Fe(VI) were 2.3-36.0-fold faster than those of Fe(VI). Free radical quenching and probe experiments revealed that the dominant active species of VUV/Fe(VI) were •OH and Fe(V)/Fe(IV), whose contribution ratios were 43.3 to 48.6% and 48.2 to 46.6%, respectively, at pH = 7.0-9.0. VUV combined with Fe(VI) not only effectively mitigated the weak oxidizing ability of Fe(VI) under alkaline conditions (especially pH = 9.0) but also attenuated the deteriorating effect of background constituents on Fe(VI). In different real waters (tap water, river water, WWTPs effluent), VUV/Fe(VI) retained a remarkably enhanced effect on CBZ degradation compared to Fe(VI). Moreover, VUV/Fe(VI) exhibited outstanding performance in the debasement of CBZ and sulfamethoxazole (SMX), as well as six other micropollutants, displaying broad-spectrum capability in degrading micropollutants. Overall, this study developed a novel oxidation process that was efficient and energy-saving for the rapid removal of micropollutants.

Analysis of contributing factors and nursing interventions for postoperative agitation following general anesthesia in thoracotomy patients.

To analyze the factors influencing agitation during emergence from general anesthesia in patients undergoing thoracotomy and to explore corresponding nursing interventions to optimize the postoperative recovery process. This study included 200 patients who underwent thoracotomy with general anesthesia at our hospital between January 12, 2022, and June 1, 2023. After surgery, all patients were closely monitored in the Intensive Care Unit (ICU). Based on their agitation status during emergence from anesthesia, patients were divided into 2 groups: an observation group (87 cases with agitation) and a control group (113 cases without agitation). We performed univariate analysis and multivariate logistic regression to identify risk factors for agitation. Based on these findings, we proposed targeted nursing strategies to address the causes of agitation, prevent complications, and meet patient care needs. Univariate analysis showed significant differences between the observation and control groups regarding age, propofol dosage, duration of surgery, infusion volume, and preoperative cognitive dysfunction (P < .05). Multivariate logistic regression identified 3 key risk factors: age over 60 years, surgery duration over 2 hours, and preoperative cognitive dysfunction. Based on these findings, we developed targeted nursing strategies to reduce the incidence of agitation and promote smooth recovery. Agitation during emergence from general anesthesia in patients undergoing thoracotomy is closely related to factors such as age and surgery duration. Developing personalized nursing plans based on these factors can enhance postoperative monitoring and care, thereby reducing agitation and improving recovery quality.

Analyzing the differences and correlations between key metabolites and dominant microorganisms in different regions of Daqu based on off-target metabolomics and high-throughput sequencing.

Daqu is usually produced in an open environment, which makes its quality unstable. The microbial community of Daqu largely determines its quality. Therefore, in order to improve the fermentation characteristics of Daqu, samples were collected from Jinsha County (MT1), Xishui County (MT2), and Maotai Town (MT3) in Guizhou Province to explore the microbial diversity of Daqu and its impact on Daqu's metabolites.Off-target metabolomics was used to detect metabolites, and high-throughput sequencing was used to detect microorganisms. Metabolomics results revealed that MT1 and MT2 had the highest relative fatty acid content, whereas MT3 had the highest organooxygen compound content. Principal component analysis and partial least squares discriminant analysis revealed significant differences in the metabolites among the three groups, followed by the identification of 33 differential metabolites (key metabolites) filtered using the criteria of variable importance in projection >1 and p < 0.001. According to the microbiological results, Proteobacteria was the dominant bacteria phylum in three samples. Gammaproteobacteria was the dominant class in MT1(26.84 %) and MT2(36.54 %), MT3 is Alphaproteobacteria(25.66 %). And Caulobacteraceae was the dominant family per the abundance analysis, MTI was 24.32 %, MT2 and MT3 were 33.71 % and 24.40 % respectively. Three samples dominant fungi phylum were Ascomycota, and dominant fungi family were Thermoascaceae. Pseudomonas showed a significant positive connection with various fatty acyls, according to correlation analyses between dominant microorganisms (genus level) and key metabolites. Fatty acyls and Thermomyces showed a positive correlation, but Thermoascus had the reverse relation. These findings offer a theoretical framework for future studies on the impact of metabolites on Baijiu quality during fermentation.

Enhanced Nitric Oxide Delivery Through Self-Assembling Nanoparticles for Eradicating Gram-Negative Bacteria.

In the current battle against antibiotic resistance, the resilience of Gram-negative bacteria against traditional antibiotics is due not only to their protective outer membranes but also to mechanisms like efflux pumps and enzymatic degradation of drugs, underscores the urgent need for innovative antimicrobial tactics. Herein, this study presents an innovative method involving the synthesis of three furoxan derivatives engineered to self-assemble into nitric oxide (NO) donor nanoparticles (FuNPs). These FuNPs, notably supplied together with polymyxin B (PMB), achieve markedly enhanced bactericidal efficacy against a wide spectrum of bacterial phenotypes at considerably lower NO concentrations (0.1-2.8 µg mL-1), which is at least ten times lower than the reported data for NO donors (≥200 µg mL-1). The bactericidal mechanism is elucidated using confocal, scanning, and transmission electron microscopy techniques. Neutron reflectometry confirms that FuNPs initiate membrane disruption by specifically engaging with the polysaccharides on bacterial surfaces, causing structural perturbations. Subsequently, PMB binds to lipid A on the outer membrane, enhancing permeability and resulting in a synergistic bactericidal action with FuNPs. This pioneering strategy underscores the utility of self-assembly in NO delivery as a groundbreaking paradigm to circumvent traditional antibiotic resistance barriers, marking a significant leap forward in the development of next-generation antimicrobial agents.

Proteogenomic Identification and Analysis of KIF5B as a Prognostic Signature for Hepatocellular Carcinoma.

BACKGROUND: Metabolic disorders are significant risk factors for liver cancer, particularly Hepatocellular Carcinoma (HCC). However, the molecular genetic basis of metabolic reprogramming in the liver remains largely uncertain. OBJECTIVE: This study aimed to investigate some novel prognostic biomarkers in HCC by using proteogenomic and transcriptomic analysis and explore the potential role of specific prognostic genes in HCC. METHODS: Here, we have presented a proteogenomic analysis of 10 pairs of HCC. Protein co-expression and pathway analysis were performed to investigate the biological characteristics of HCC. Protein and mRNA expression profiles of multi-cohorts were integrated to detect novel prognostic protein markers of HCC. The carcinogenic roles of candidate prognostic markers were further evaluated by MTS assay, colony formation, monolayer wound healing assay, and xenograft models. RESULTS: A total of 2086 proteins with significantly different expressions were detected in HCC. Pathways related to oncogenic signaling and insulin-related metabolism have been found to be dysregulated and differentially regulated in HCC. We have identified the novel prognostic biomarkers, KIF5B, involved in liver metabolic reprogramming. The biomarkers were identified using multivariable COX regression analysis from two independent proteomic datasets (Fudan Cohort and our recruited cohort) and the TCGA mRNA database. Both the protein and mRNA up-regulation of KIF5B have been found to be associated with a poor clinical outcome in HCC. Insulin activated the protein expression of KIF5B in HCC. Knocking out KIF5B expression by sgRNA decreased the protein expression of FASN and SCD1 and the intracellular triglyceride concentration. Silencing KIF5B suppressed HCC cell proliferation and colony formation in vitro, as well as HCC growth in xenograft models. CONCLUSION: Our findings have suggested KIF5B protein to function as a novel prognostic biomarker in HCC. KIF5B expression has been found to activate the AKT/mTOR pathway and reprogram triglyceride metabolism, leading to HCC development. Targeting KIF5B may be an effective strategy in the clinical treatment of HCC.

Improved the physicochemical properties and bioactivities of oligosaccharides by degrading self-extracting/commercial ginseng polysaccharides.

Degradation of polysaccharides is an effective method to improve the physicochemical properties and biological activities. In this study, self-extracting ginseng oligosaccharides (SGOs) and commercial ginseng oligosaccharides (CGOs) were compared with self-extracting ginseng polysaccharides (SGPs) and commercial ginseng polysaccharides (CGPs). The four saccharides were composed of different types and proportions of monosaccharides. And the molecular weight (Mw) size order was SGP > CGP > CGO > SGO. The SGO and CGO had better solubility with smaller particle size, 97.63 ± 0.42 % and 96.23 ± 1.12 %, respectively. Fourier transform infrared, nuclear magnetic resonance, and X-ray diffraction spectroscopy characterized the structures of four saccharides. It was found that the structural features of saccharides did not change after enzymatic hydrolysis. The results of bioactivities showed that SGO and CGO had better antioxidant, hypoglycemic, and hypolipidemic activities. Compared with polysaccharides, oligosaccharides could significantly promote the proliferation and phagocytic ability of RAW 264.7 cells. Oligosaccharides induced RAW 264.7 cells to produce more NO and had better immune activity. Pearson's correlation coefficient analysis confirmed the bioactivities were negatively correlated with the Mw of ginseng saccharides. This study suggests that reducing the Mw of saccharides is an effective strategy to enhance their bioactivities.

The evaluation of next-generation probiotics on broiler growth performance, gut morphology, gut microbiome, nutrient digestibility, in addition to enzyme production of Bacillus spp. in vitro.

Considerable research has been conducted into the efficacy of individual probiotics in broiler production, however information on the most effective combinations of synergistic Bacillus probiotic is lacking. This study investigated the impact of different Bacillus strain combinations in broiler chickens, as well as in vitro enzyme production. In experiment one, a total of 576 Ross 308 broilers at 1 d old were grown for 21 d across 6 treatments of maize-soybean diets (n = 12 pens per treatment) to compare three different strain combinations (formulation 1 [F1]: 3 strains Bacillus amyloliquefaciens; F2: Bacillus coagulans and 2 strains B. amyloliquefaciens; F3: B. coagulans, Bacillus licheniformis and 2 strains B. amyloliquefaciens; F5: Bacillus subtilis, B. licheniformis and 2 strains B. amyloliquefaciens), positive control (PC), and a negative control antibiotic treatment group (NC). In Exp. 2, a total of 360 one-day-old ROSS308 broilers were used to test five treatments (n = 9) including PC, NC, F1 and F5 (selected from Exp. 1), and F4 (Bacillus pumilis and 2 strains B. amyloliquefaciens) in a maize-soybean diet. B. amyloliquefaciens F1 demonstrated a significant improvement in feed conversion ratio (FCR) compared to F2 at d 14 (1.49 vs 2.10; P = 0.038) and the body weight (BW) at d 21 (847.0 g vs 787.4 g) compared to other combinations (P = 0.027). The FCR at d 21 tended to be lower in birds fed F1 (1.46 vs 1.66) compared to the control (P = 0.068). Probiotic treatments had significantly improved nutrient digestibility compared to the PC and NC. Also, probiotic treatments supported the growth of Streptococcus, a common commensal genus and reduced the abundance of genera that correlated with low weight gain such as Akkermansia. Experiment two revealed that F4 improved FCR (P < 0.001) and BW at 28 d (P = 0.014). In vitro testing showed a high production of protease and amylase by Bacillus. Thus, the addition of Bacillus probiotics, particularly containing B. amyloliquefaciens strains and Bacillus pumilus, into the diet of broiler chickens improves production performance, nutrient digestibility, and allows the proliferation of beneficial gut microbiota.

Associations between structural neuroimaging markers of Alzheimer's risk and scam susceptibility.

Older adults with greater scam susceptibility are at greater risk for mild cognitive impairment and incident Alzheimer's dementia, regardless of baseline cognition. This, combined with documented associations between scam susceptibility and beta amyloid at death suggests that scam susceptibility may be an earlier indicator of pathological aging than cognition. Little, however, is known about whether in vivo neuroimaging markers of early-stage risk for Alzheimer's dementia are also related to scam susceptibility; such knowledge will inform upon the associations of neurodegenerative processes with scam susceptibility and may help identify vulnerable individuals. Participants were 472 community-based adults without dementia (age ~ 81y; 75% women) from the Rush Memory and Aging Project. Baseline 3T MRI T1-weighted structural and T2-weighted FLAIR data were used to assess the cortical thickness 'signature' of Alzheimer's disease (AD-CT) and white matter hyperintensity (WMH) burden, respectively. Scam susceptibility was measured using a questionnaire that assessed behaviors associated with vulnerability to fraud and scams. Demographically-adjusted linear effects regression models determined the relationship of each neuroimaging measure, first separately and then combined, with scam susceptibility. Reduced AD-CT was associated with higher levels of scam susceptibility (estimate=-0.10, standard error = 0.03, p = 0.002). WMH burden was not associated with scam susceptibility either alone or when combined in the same model as AD-CT (p-values ≥ 0.14). Results for AD-CT persisted after the inclusion of WMH burden. AD-CT was associated with scam susceptibility in older adults without dementia possibly signaling an in vivo profile of this behavior.

Decitabine consolidation after CD19/CD22 CAR-T therapy as a novel maintenance treatment significantly improves survival outcomes in relapsed/refractory B-ALL patients.

OBJECTIVE: We aimed to evaluate the efficacy of decitabine consolidation after treatment with CD19/CD22 chimeric antigen receptor T-cell (CAR-T) for patients with relapsed/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL). METHODS: We retrospectively analysed 48 patients with r/r B-ALL who received CD19/CD22 CAR-T therapy between September 2017 and May 2021. Sixteen patients received decitabine consolidation (20 mg/m2/day for 5 days at 3-month intervals) after CAR-T therapy (DAC group), while 32 patients did not receive decitabine consolidation (CON group). Overall survival (OS), leukaemia-free survival (LFS), and cumulative incidence of relapse (CIR) were evaluated in both groups. Time-to-event analysis was performed using the Kaplan-Meier method. RESULTS: The median follow-up periods in the DAC and CON groups were 41.2 months and 28.6 months, respectively. The 4-year OS and 4-year LFS rates in both groups were 93.3 % and 64.3 % (P=0.029) and 87.5 % and 55.9 % (P=0.059), respectively. The 1-year CIR was 6.25 % and 28.6 %, respectively. Univariate and multivariate Cox regression analyses showed that decitabine consolidation after CAR-T therapy was significantly associated with superior OS (hazard ratio [HR]: 0.121, 95 % confidence interval [CI]: 0.015-0.947, P=0.044), and bridging to haematopoietic stem cell transplantation after CAR-T therapy was significantly associated with superior LFS (HR: 0.279, 95 %CI: 0.093-0.840, P=0.023). CONCLUSIONS: Our study recommends decitabine consolidation after CD19/CD22 CAR-T therapy as a novel maintenance strategy to improve the survival outcomes of patients with r/r B-ALL.

Engineering Oncogenic Hotspot Mutations on SF3B1 via CRISPR-Directed PRECIS Mutagenesis.

SF3B1 is the most recurrently mutated RNA splicing gene in cancer. However, research of its pathogenic role has been hindered by a lack of disease-relevant cell line models. Here, our study compared four genome engineering platforms to establish SF3B1 mutant cell lines: CRISPR-Cas9 editing, AAV homology-directed repair editing, base editing (ABEmax, ABE8e), and prime editing (PE2, PE3, PE5max). We showed that prime editing via PE5max achieved the most efficient SF3B1 K700E editing across a wide range of cell lines. Our approach was further refined by coupling prime editing with a fluorescent reporter that leverages a SF3B1 mutation-responsive synthetic intron to mark successfully edited cells. By applying this approach, called prime editing coupled intron-assisted selection (PRECIS), we introduced the K700E hotspot mutation into two chronic lymphocytic leukemia cell lines, HG-3 and MEC-1. We demonstrated that our PRECIS-engineered cells faithfully recapitulate known mutant SF3B1 phenotypes, including altered splicing, copy number variations, and cell-growth defect. Moreover, we discovered that the SF3B1 mutation can cause the loss of Y chromosome in chronic lymphocytic leukemia. Our results showcase that PRECIS is an efficient and generalizable method for engineering genetically faithful SF3B1 mutant models. Our approach provides new insights on the role of SF3B1 mutation in cancer and enables the generation of SF3B1 mutant cell lines in relevant cellular context. SIGNIFICANCE: This study developed an approach that can reliably and efficiently engineer SF3B1 mutation into different cellular contexts, thereby revealing novel roles of SF3B1 mutation in driving aberrant splicing, clonal evolution, and genome instability.

Rhodium(I)-Catalyzed Cascade Annulation of 1,n-Diynyl Nitrones to 3,4-Fused Fully Substituted Furans.

A method for the assembly of fully substituted furans containing a 3,4-fused 5-8-membered carbocycle, heterocycle, or spirocycle from rhodium(I)-catalyzed and 1,1,1,3,3,3-hexafluoroisopropanol (HFIP)-assisted cascade annulation of 1,n-diynyl nitrones has been developed.

Association Between Sarcopenia, Clinical Outcomes, and Survival in Patients with Extensive-Stage Small Cell Lung Cancer Treated with First-Line Immunochemotherapy: A Prospective Cohort Study.

OBJECTIVE: To investigate the association between sarcopenia, short-term efficacy, and long-term survival in patients with extensive small-cell lung cancer (SCLC) treated with standard first-line immunochemotherapy. METHODS: A total of 63 patients initially diagnosed with extensive-stage small cell lung cancer were enrolled in the prospective study from December 1, 2020 to December 31, 2022. The clinical characteristics, body composition, blood test results, and image data were obtained before treatment. Patients were divided into sarcopenia and non-sarcopenia groups according to the diagnostic criteria of the Asian Sarcopenia Working Group 2019. The primary outcome was overall survival (OS) and comprehensive survival analyses were performed. Secondary outcomes included short-term efficacy and adverse events associated with first-line immunochemotherapy. RESULTS: The median age of the 63 patients enrolled in our study was 63.0 years (40-80 years). The incidence of sarcopenia was 19.0% (12/63) in patients with extensive SCLC. Compared with non-sarcopenia patients, extensive-stage SCLC patients with sarcopenia were significantly older (69.0 vs. 62.0, P = 0.017), and had lower body mass index (BMI) (20.29 vs. 24.27, P < 0.001), hand grip strength (HGS) (20.42 vs. 30.75, P < 0.001), and albumin (35.9 vs. 41.40, P < 0.001). The objective response rate after two cycles of standard first-line immunochemotherapy in the sarcopenia group was lower than in the non-sarcopenia group (30.0 vs. 78.9%, P = 0.012). There was no significant difference in chemotherapy-related hematological toxicity between the two groups. During a median follow-up of 15 months (3-33 months), patients with extensive SCLC had a median OS of 24 months, with 1-year survival of 75% and 2-year survival of 52%, respectively. Compared to non-sarcopenia patients, the median OS in the sarcopenia group was significantly shorter (9 vs. 24 months, P = 0.0014). Multivariate Cox analysis showed that sarcopenia was an independent risk factor for OS in patients with extensive SCLC (HR = 4.993, 95%CI = 1.106-22.538, P = 0.037). CONCLUSIONS: Patients with Extensive SCLC and sarcopenia had worse clinical outcomes and shorter OS. Sarcopenia is a prognostic factor affecting first-line treatment efficacy and long-term survival of patients with SCLC in the era of immunotherapy.

Clinicopathologic and prognostic implications of HOXA gene and its associated long-noncoding RNAs expression in non-small cell carcinoma: A meta-analysis.

BACKGROUND: We conducted an investigation into the correlation between HOXA and associated long-noncoding RNAs, along with their clinicopathologic and prognostic features in non-small cell lung cancer (NSCLC). METHODS: A comprehensive search across multiple electronic databases, including PubMed and the Web of Science, was conducted to identify relevant studies. The association between HOXA, clinicopathologic parameters, and prognosis was assessed using relative risk (RR) and hazard ratio (HR) with a 95% confidence interval (CI). Data compilation was performed using STATA 12.0 software. RESULTS: A total of 11 trials involving 2058 patients with NSCLC were included in our study. Significant correlations were observed between HOXA-AS2 and TNM stage (III-IV) (RR=2.173, 95% CI: 1.386-5.437, P< 0.05) and HOTTIP and age (≥60-year-old) (RR=2.628, 95% CI: 1.185-5.829, P< 0.05) and non-smoking (RR=0.387, 95% CI: 0.156-0.959, P< 0.05). The combined results indicated a significant association between HOXA5 and increased overall survival (HR = 0.69, 95% CI = 0.57-0.84, P < .001). Additionally, HOXA-AS2, HOXA11 and HOTTIP were identified as potential independent predictors for poorer OS (HOXA-AS2: HR =3.48, 95% CI = 1.95 to 6.21, P < 0.05; HOXA11: HR=1.39, 95%CI = 1.08 to 1.79, P < 0.05; HOTTIP: HR=2.44, 95%CI = 1.10 to 5.42, P < 0.05). The prognostic significance of HOXA1, HOXA3 and HOXA4 was uncertain (HOXA1: HR=1.40, 95% CI =0.28 to 7.06, P > 0.05; HOXA3: HR=1.20, 95% CI = 0.96 to 1.50, P > 0.05; HOXA4: HR=0.97, 95% CI = 0.77 to 1.23, P > 0.05). CONCLUSIONS: The HOXA gene family has some potential to emerge as a novel prognostic factor for NSCLC and is correlated with some clinicopathological parameters such as the TNM stage, age and smoking. However, further meticulously designed prospective studies are warranted to substantiate these findings.

Understanding Variations in Ferrate Detection through the ABTS Method in the Presence of Electron-Rich Organic Compounds.

The chromogenic reaction between 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) and ferrate [Fe(VI)] has long been utilized for Fe(VI) content measurement. However, the presence of electron-rich organic compounds has been found to significantly impact Fe(VI) detection using the ABTS method, leading to relative errors ranging from ∼88 to 100%. Reducing substances consumed ABTS•+ and resulted in underestimated Fe(VI) levels. Moreover, the oxidation of electron-rich organics containing hydroxyl groups by Fe(VI) could generate a phenoxyl radical (Ph•), promoting the transformation of Fe(VI) → Fe(V) → Fe(IV). The in situ formation of Fe(IV) can then contribute to ABTS oxidation, altering the ABTS•+:Fe(VI) stoichiometry from 1:1 to 2:1. To overcome these challenges, we introduced Mn(II) as an activator and 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic agent for Fe(VI) detection. This Mn(II)/TMB method enables rapid completion of the chromogenic reaction within 2 s, with a low detection limit of approximately 4 nM and a wide detection range (0.01-10 µM). Importantly, the Mn(II)/TMB method exhibits superior resistance to reductive interference and effectively eliminates the impact of phenoxyl-radical-mediated intermediate valence iron transfer processes associated with electron-rich organic compounds. Furthermore, this method is resilient to particle interference and demonstrates practical applicability in authentic waters.

A novel nomogram for predicting optimal weight loss response following diet and exercise intervention in patients with obesity.

This study aimed to identify factors associated with optimal weight loss response by analyzing pre-weight loss data from a cohort of 2577 patients with obesity who visited weight management clinics between 2013 and 2022. Out of these, 1276 patients had follow-up data available. Following dietary and exercise interventions, 580 participants achieved optimal weight loss outcomes. Participants were subsequently divided into two groups based on their weight loss outcomes: those who achieved optimal weight loss response and those who did not. Statistical analysis, conducted using RStudio, identified thirteen predictor variables through LASSO and logistic regression, with age emerging as the most influential predictor. A nomogram was developed to predict optimal weight loss response, showing good predictive performance (AUC = 0.807) and clinical applicability, validated by internal validation methods. Decision curve analysis (DCA) further illustrated the nomogram's clinical utility. The developed nomogram prediction model for optimal weight loss response is user-friendly, highly accurate, and demonstrates excellent discriminative and calibration capabilities.

Comparative evaluation of fermented ginseng on alleviating antibiotic-associated diarrhea in mice.

Antibiotic associated diarrhea (AAD) was a common side effect of antibiotics, and fermented ginseng exhibited potential in treating AAD. In this study, the effects of fermented red, white, and black ginseng on AAD were investigated, with a focus on intestinal flora and inflammation. Clindamycin was used to induce AAD in mice, which caused severe diarrhea and weight loss. However, treatment with fermented ginseng effectively alleviated diarrhea, and reduced inflammation in colonic serosal tissue, thereby mitigating antibiotic-induced intestinal tissue damage. 16S rRNA sequencing revealed that clindamycin disrupted the Bacteroides/Firmicutes ratio (P < 0.001), which was reversed by fermented ginseng treatment. Furthermore, inflammatory cytokines like IL-1ß, IL-6, and TNF-α significantly decreased (P < 0.05) after clindamycin treatment but returned to normal levels following fermented ginseng treatment. In conclusion, fermented red, white, or black ginseng (at a dosage of 0.5 g/kg) exhibited efficacy against AAD in mice, reinstating gut flora balance and easing inflammation.

Self-Produced O2 CNs-Based Nanocarriers of DNA Hydrophobization Strategy Triggers Photodynamic and Mitochondrial-Derived Ferroptosis for Hepatocellular Carcinoma Combined Treatment.

Hypoxia can aggravate tumor occurrence, development, invasion, and metastasis, and greatly inhibit the photodynamic therapy (PDT) effect. Herein, carbon nitride (CNs)-based DNA and photosensitizer co-delivery systems (BPSCNs) with oxygen-producing functions are developed to address this problem. Selenide glucose (Seglu) is used as the dopant to prepare red/NIR-active CNs (SegluCNs). The tumor-targeting unit Bio-PEG2000 is utilized to construct BPSCNs nanoparticles through esterification reactions. Furthermore, DNA hydrophobization is realized via mixing P53 gene with a positively charged mitochondrial-targeted near-infrared (NIR) emitting photosensitizer (MTTPY), which is encapsulated in non-cationic BPSCNs for synergistic delivery. Ester bonds in BPSCNs@MTTPY-P53 complexes can be disrupted by lipase in the liver to facilitate P53 release, upregulated P53 expression, and promoted HIF-1α degradation in mitochondria. In addition, the oxygen produced by the complexes improved the hypoxic microenvironment of hepatocellular carcinoma (HCC), synergistically downregulated HIF-1α expression in mitochondria, promoted mitochondrial-derived ferroptosis and enhanced the PDT effect of the MTTPY unit. Both in vivo and in vitro experiments indicated that the transfected P53-DNA, produced O2 and ROS by these complexes synergistically led to mitochondrial-derived ferroptosis in hepatoma cells through the HIF-1α/SLC7A11 pathway, and completely avoiding PDT resistance caused by hypoxia, exerting a significant therapeutic role in HCC treatment.