Metabolomics for hematologic malignancies: Advances and perspective.

With the use of advanced technology, metabolomics allows for a thorough examination of metabolites and other small molecules found in biological specimens, blood, and tissues. In recent years, metabolomics has been recognized that is closely related to the development of malignancies in the hematological system. Alterations in metabolomic pathways and networks are important in the pathogenesis of hematologic malignancies and can also provide a theoretical basis for early diagnosis, efficacy evaluation, accurate staging, and individualized targeted therapy. In this review, we summarize the progress of metabolomics, including glucose metabolism, amino acid metabolism, and lipid metabolism in lymphoma, myeloma, and leukemia through specific mechanisms and pathways. The research of metabolomics gives a new insight and provides therapeutic targets for the treatment of patients with hematologic malignancies.

Development and validation of a novel vault prediction formula based on structural parameters of the anterior and posterior chambers.

BACKGROUND: Accurate prediction of postoperative vault in implantable collamer lens (ICL) implantation is crucial; however, current formulas often fail to account for individual anatomical variations, leading to suboptimal visual outcomes and necessitating improved predictive models. We aimed to verify the prediction accuracy of our new predictive model for vaulting based on anterior and posterior chamber structural parameters. METHODS: This retrospective observational study included 137 patients (240 eyes) who previously underwent ICL surgery. Patients were randomly divided into the model establishment (192 eyes) or validation (48 eyes) groups. Preoperative measurements of the anterior and posterior chamber structures were obtained using Pentacam, CASIA2 anterior segment optical coherence tomography (AS-OCT), ultrasound biomicroscopy, and other devices. Stepwise multiple linear regression analysis was used to evaluate the relationship between the vault and each variable (WL formula). The Friedman test was performed for the vaulting prediction results of the WL, NK (Ver. 3), and KS formulas (Ver. 4) in CASIA2 AS-OCT, as well as the Zhu formula and vault measurements. The proportions of prediction error within ± 250 µm per formula were compared. RESULTS: The predicted vault values of the WL, NK, KS, and Zhu formulas and vault measurements were 668.74 ± 162.12, 650.85 ± 248.47, 546.56 ± 128.99, 486.56 ± 210.76, and 716.06 ± 233.84 µm, respectively, with a significant difference (χ2 = 69.883, P = 0.000). Significant differences were also found between the measured vault value and Zhu formula, measured vault value and KS formula, WL formula and Zhu formula, WL formula and KS formula, NK formula and KS formula, and NK formula and Zhu formula (P < 0.001) but not between other groups. The proportions of prediction error within ± 250 µm per formula were as follows: WL formula (81.3%) > NK formula (70.8%) > KS formula (66.7%) > Zhu formula (54.2%). CONCLUSIONS: The WL formula, which considers the complexity of the anterior and posterior chamber structures, demonstrates greater calculation accuracy, compared with the KS (Ver. 4) and Zhu formulas. The proportion of absolute prediction error ≤ 250 µm is higher with the WL formula than with the NK formula (ver. 3). This enhanced predictive capability can improve ICL sizing decisions, thereby increasing the safety and efficacy of ICL implantation surgeries.

Mitigating N2O emissions in land treatment systems: Mechanisms, influences, and future directions.

Land treatment systems (LTS) are widely used in decentralized domestic wastewater treatment due to low energy requirements and effective treatment outcomes. However, LTS operations are also a significant source of N2O emissions, a potent greenhouse gas threatening the ozone layer and posing risks to human health. Despite the importance of understanding and controlling N2O emissions, existing literature lacks comprehensive analyses of the mechanisms driving N2O generation and effective control strategies within LTS. This study addresses this gap by reviewing current research and identifying key factors influencing N2O emissions in LTS. This review reveals that in addition to traditional nitrification and denitrification processes, co-denitrification and complete ammonia oxidation are crucial for microbial nitrogen removal in LTS. Plant selection is primarily based on their nitrogen absorption capacity while using materials such as biochar and iron can provide carbon sources or electrons to support microbial activities. Optimizing operational parameters is essential for reducing N2O emissions and enhancing nitrogen removal efficiency in LTS. Specifically, the carbon-to­nitrogen ratio should be maintained between 5 and 12, and the hydraulic loading rate should be kept within 0.08-0.2 m3/(m2·d). Dissolved oxygen and oxidation-reduction potential should be adjusted to meet the aerobic or anaerobic conditions the microorganisms require. Additionally, maintaining a pH range of 6.5-7.5 by adding alkaline substances is crucial for sustaining nitrous oxide reductase activity. The operating temperature should be maintained between 20 and 30 °C to support optimal microbial activity. This review further explores the relationship between environmental factors and microbial enzyme activity, community structure changes, and functional gene expression related to N2O production. Future research directions are proposed to refine N2O flux control strategies. By consolidating current knowledge and identifying research gaps, this review advances LTS management strategies that improve wastewater treatment efficiency while mitigating the environmental and health impacts of N2O emissions.

Increasing cotton lint yield and water use efficiency for subsurface drip irrigation without mulching.

Introduction: Planting without mulching can eliminate the residual film pollution caused by the long-term use of plastic film covers, but it will increase soil moisture evaporation and heat loss and severely reduce water use efficiency and cotton productivity in cotton (Gossypium hirsutum L.) fields in arid regions. It is unclear whether the advantages of subsurface drip irrigation and nighttime irrigation can be leveraged to reduce the amount of irrigation applied in fields, improve the soil and leaf hydrothermal environments, and increase the synchronicity of yield and water use efficiency (WUE). Methods: Therefore, in a two-year field experiment (2019-2020), cotton was grown under different irrigation treatments (I5, 3753 m3 ha-1; I4, 3477 m3 ha-1; I3, 3201 m3 ha-1; I2, 2925 m3 ha-1; and I1, 2649 m3 ha-1). The soil volumetric moisture content, soil temperature, leaf relative water content (RWC), daily changes in gas exchange parameters, lint yield, and WUE were evaluated. Results and discussion: The results showed that reducing irrigation can reduce the soil volumetric moisture content (0-40 cm soil layer), increase the soil temperature and soil temperature conductivity, and increase the leaf temperature, intercellular carbon dioxide concentration (Ci), and WUE; however, reducing irrigation is not conducive to increasing the leaf RWC, net photosynthetic rate (Pn), stomatal conductance (Gs), or transpiration rate (Tr). There was no significant difference in WUE between the I3 and I4 treatments from 8:00 to 20:00, but the lint yield in these treatments increased by 2.8-12.2% compared to that in the I5 treatment, with no significant difference between the I3 and I4 treatments. In addition, a related analysis revealed that the positive effects of the leaf hydrothermal environment on the Pn and soil temperature on the WUE occurs during the same period (10:00-16:00). Overall, an irrigation amount of 3201-3477 m3 ha-1 applied with a subsurface nighttime irrigation system without mulching can enhance the soil moisture content and soil temperature, maintain a high photosynthetic capacity, and increase the lint yield and WUE. These results revealed that the negative impacts of plastic film contamination in arid areas can be alleviated.

First Report of Rugonectria rugulosa Causing Dieback of Prunus salicina "Banbianhong" in China.

Banbianhong (Prunus salicina) is a valuable fruit crop cultivated in the southwestern regions of China for its high quality fruit and substantial economic benefits (Wang et al. 2021). In July 2023, dieback disease was observed in Banbianhong in Suijiang County, Zhaotong, Yunnan Province, with an incidence of up to 10%. The disease caused brownish nodules in the cortex of the infected plant, leading to dry cracking, and exposing grayish-brown xylem, which caused the plant to wither and die. Upon longitudinal cutting of twigs, lesions were evident and characterized by browning and necrosis of the cauline bundle and pith within the tissue. The diseased tissues were sectioned into 2 mm2 pieces and surface disinfected with 70% ethanol and 1% NaClO and rinsed with double distilled water. The tissue fragments were plated onto potato dextrose agar (PDA), and incubated for 7 days at 28°C. A total of six isolates were obtained, and two isolates (WG2-1 and WG2-3) were selected for morphological, molecular identification and pathogenicity testing. On PDA, the colony diameter of WG2-1 and WG2-3 were recorded as 5.50±0.56 mm/day and 6.08±0.37 mm/day, respectively. The microconidia of both isolates were zero-septate, smooth, greenish, subglobose to ellipsoidal, and measured 5 to 10 × 1.5 to 3 µm (n = 50) in size. However, macroconidia were not observed. The internal transcribed spacer rDNA (ITS) and ß-tubulin 2 (TUB2) genes were amplified using the primer pairs ITS1/4 (White et al. 1989) and Bt2a/2b (Glass and Donaldson 1995). BLAST analysis of the obtained ITS sequences (accession Nos. PP581792) and TUB2 sequences (accession Nos. PP2815212) sequences showed 100% identity with Rugonectria rugulosa (accession nos. MG991753 for ITS and KM232007 for TUB2). Based on these characteristics, the isolates have been identified as R. rugulosa and have been deposited in the Agricultural Environment and Resource Research Institute plant pathogen lab at Yunnan Academy of Agricultural Sciences. In this study, Pathogenicity tests were conducted on one-year-old Prunus salicina "Banbianhong" twigs to complete Koch's postulates. The twigs were wounded using a 1-mm sterile corking borer and 14-day-old mycelium plugs of isolate (WG2-1) were inoculated and covered with sealing films. Sterile PDA plugs were placed into the wounds of control twigs. Eighteen healthy twigs were inoculated with isolates or PDA plugs (n = 6 twigs/treatment, the size of the twigs: 8 cm length and diameter about 0.7 cm, with three replications) and were placed in a closed sterile tray with the wet filter papers in a thermostatic incubator (type, HYC-260) at 28°C, respectively. The twigs inoculated with the isolates exhibited brown lesions site of inoculation, whereas the controls remained asymptomatic. R. rugulosa was successfully reisolated from the lesions but not from these control wounds and was identified by the methods described above. R. rugulosa has been reported to be associated with the die-back disease of Falcataria moluccana in China (Wang et al. 2019). The occurrence and spread of R. rugulosa in growing areas of Prunus salicina "Banbianhong" in Suijiang county have caused severe economic losses. To our knowledge, this is the first report of the die-back disease of Prunus salicina "Banbianhong" caused by R. rugulosa. These results confirm the pathogenicity of R. rugulosa in Prunus salicina "Banbianhong" and provide valuable insights for developing disease management and prevention strategies.

Mechanical Loading Modulates AMPK and mTOR Signaling in Muscle Cells.

Skeletal muscle adaptation to exercise involves various phenotypic changes that enhance the metabolic and contractile functions. One key regulator of these adaptive responses is the activation of AMPK, which is influenced by exercise intensity. However, the mechanistic understanding of AMPK activation during exercise remains incomplete. In this study, we utilized an in vitro model to investigate the effects of mechanical loading on AMPK activation and its interaction with the mTOR signaling pathway. Proteomic analysis of muscle cells subjected to static loading (SL) revealed distinct quantitative protein alterations associated with RNA metabolism, with 10% SL inducing the most pronounced response compared to lower intensities of 5% and 2% as well as the control. Additionally, 10% SL suppressed RNA and protein synthesis while activating AMPK and inhibiting the mTOR pathway. We also found that SRSF2, necessary for pre-mRNA splicing, is regulated by AMPK and mTOR signaling, which, in turn, is regulated in an intensity-dependent manner by SL with the highest expression in 2% SL. Further examination showed that the ADP/ATP ratio was increased after 10% SL compared to the control and that SL induced changes in mitochondrial biogenesis. Furthermore, Seahorse assay results indicate that 10% SL enhances mitochondrial respiration. These findings provide novel insights into the cellular responses to mechanical loading and shed light on the intricate AMPK-mTOR regulatory network in muscle cells.

Hourly emission amounts and concentration of water-soluble ions in primary particles from residential coal burning in rural northern China.

Residential coal burning (RCB) stands as an important contributor to ambient pollutants in China. For the effective execution of air pollution control policies, it is essential to maintain precise emission inventories of RCB. The absence of hourly emission factors (EFs) combined with the inaccuracies in the spatial-temporal distribution of activity data, constrained the quality of residential coal combustion emission inventories, thereby impeding the estimation of air pollutant emissions. This study revised the hourly EFs for PM2.5 and water-soluble ions (WSIs) emitted from RCB in China. The hourly emission inventories for PM2.5 and WSIs derived from RCB illustrate the diurnal fluctuations in emission patterns. This study found that the emissions of PM2.5, NH4+, Cl-, and SO42- showed similar emission features with emission of 106.8 Gg, 1417.6, 356.8, and 5868.5 ton in erupt period. The results provide basic data for evaluating RCB emission reduction policies, simulating particles, and preventing air pollution in both sub-regions and time periods. The spatial emission and simulated concentration distribution of PM2.5 and WSIs indicated that emission hotspot shifted from North China Plain (NCP) to Northeast region in China. The emissions in China were well-controlled in '2 + 26' region (R28) priority region, with hotspots decreasing by 99.6% in BTH region. The RCB became the dominant contributor to ambient PM2.5 with a ratio in the range of 16.2-23.7% in non-priority region.

Single-Cell RNA Sequencing Reveals Transcriptional Signatures and Cell-Cell Communication in Diabetic Retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is a major cause of vision loss in workingage individuals worldwide. Cell-to-cell communication between retinal cells and retinal pigment epithelial cells (RPEs) in DR is still unclear, so this study aimed to generate a single-cell atlas and identify receptor‒ligand communication between retinal cells and RPEs. METHODS: A mouse single-cell RNA sequencing (scRNA-seq) dataset was retrieved from the GEO database (GSE178121) and was further analyzed with the R package Seurat. Cell cluster annotation was performed to further analyze cell‒cell communication. The differentially expressed genes (DEGs) in RPEs were explored through pathway enrichment analysis and the protein‒ protein interaction (PPI) network. Core genes in the PPI were verified by quantitative PCR in ARPE-19 cells. RESULTS: We observed an increased proportion of RPEs in STZ mice. Although some overall intercellular communication pathways did not differ significantly in the STZ and control groups, RPEs relayed significantly more signals in the STZ group. In addition, THBS1, ITGB1, COL9A3, ITGB8, VTN, TIMP2, and FBN1 were found to be the core DEGs of the PPI network in RPEs. qPCR results showed that the expression of ITGB1, COL9A3, ITGB8, VTN, TIMP2, and FBN1 was higher and consistent with scRNA-seq results in ARPE-19 cells under hyperglycemic conditions. CONCLUSION: Our study, for the first time, investigated how signals that RPEs relay to and from other cells underly the progression of DR based on scRNA-seq. These signaling pathways and hub genes may provide new insights into DR mechanisms and therapeutic targets.

Protection of Omicron Sub-Lineage Infection Against Reinfection with Another Omicron Sub-Lineage: Systematic Review, Meta-Analysis, and Meta-Regression - Worldwide, 2022-2023.

What is already known about this topic?: Both the decline in immunity over time and the evolution of the virus play a role in the level of protection offered by a prior infection. What is added by this report?: Point estimates indicated variations in protection levels based on the initial infecting variant and the reinfecting variant. There was a consistent correlation between real-world protection, antigenic distance, and humoral immunity levels. Specifically, shorter antigenic distances and higher humoral immunity levels corresponded to enhanced real-world protection. What are the implications for public health practice?: Our findings suggest that virological and immunological studies could help identify and assess the epidemic risk posed by new variants before they become dominant. Prompt incorporation of the latest variants into the antigen components of the coronavirus disease 2019 (COVID-19) vaccines can significantly contribute to effective epidemic prevention and control measures.

Gaussian Process Regression for State-to-State Integral Cross Sections: The Case of the O + O2 Collision Dissociation Reactions.

Research on hypersonic vehicles has become increasingly important worldwide in recent years. However, accurately simulating the dynamics of the nonequilibrium high-temperature reactions that are in the hypersonic flow around the vehicles presents a significant challenge as a large number of states and transitions are accessible even for the smallest atom-diatom reaction systems. It is quite difficult, sometimes even impossible, to exhaustively investigate all relevant combinations or determine high-dimensional analytical representations for the state-to-state reaction probabilities. In this study, we used Gaussian process regression (GPR) to fit a model based on only 807 QCT data for training. The confidence interval of the GPR prediction and the Kullback-Leibler (KL) divergence were used to help minimize the sampling amount of data for fitting the converged GPR model. The model aims to predict the state-to-state integral cross section (ICS) of the O + O2 → 3O dissociation reaction under random initial conditions (Et, v, j). In total, it took almost a month to obtain this converged GPR model, but it took only a few seconds to predict the ICS value for any initial condition. For 330 initial conditions not included in the training set, the mean-square error (MSE) between the QCT-calculated ICSs and the GPR-predicted ones is only 0.08 Å2 and the R2 is 0.9986, indicating that the GPR model can replace the direct expensive QCT calculation with high accuracy. Finally, we calculated the equilibrium dissociation rate coefficients based on the StS ICS values predicted by the GPR model, and the results were in good agreement with available experimental and theoretical results. Thus, this study provides an effective and accurate approach to the extensive direct state-to-state reaction dynamic calculations.

Portable electrochemical sensing platform based on amidated GO-MOF and PEDOT:PSS for high-efficient detection of ponceau 4R.

A promising electrochemical sensing platform for the detection of ponceau 4R in food has been fabricated based on the carboxylated graphene oxide (GO-COOH), metal-organic framework (MOF) UIO-66-NH2, and poly (3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). To this end GO-COOH was covalently coupled with UIO-66-NH2 through amide reaction, endowing the material (GO-CONH-UIO-66) unique hierarchical pores and high chemical stability and as a result improving the conductivity of MOF and the dispersion of GO. After the addition of PEDOT:PSS into GO-CONH-UIO-66, the continuity and conductivity of the composite (PEDOT:PSS/GO-CONH-UIO-66) have been further enhanced, due to the high conductivity, favorable film-forming, and hydrophilic properties of PEDOT:PSS. Systematic electrochemical experiments confirm that the PEDOT:PSS/GO-CONH-UIO-66/GCE shows satisfactory electrochemical sensing properties towards the detection of ponceau 4R, with a wide linear detection range of 0.01-30 µM, a low limit of detection of 3.33 nM, and a high sensitivity of 0.606 µA µM-1 cm-2. The PEDOT:PSS/GO-CONH-UIO-66 sensing platform was successfully used to detect ponceau 4R in beverage, and the detection results were compared with  high-performance liquid chromatography. As a result, the PEDOT:PSS/GO-CONH-UIO-66 composite shows a promising application prospect for rapid detection of ponceau 4R in food and will play significant role in food safety detection and supervision.

Identification of coagulation diagnostic biomarkers related to the severity of spinal cord injury.

BACKGROUND: Blood always shows coagulation changes after spinal cord injury (SCI), and identifying these blood changes may be helpful for diagnosis and treatment of SCI. Nevertheless, studies to date on blood coagulation changes after SCI in humans are not comprehensive. Therefore, this study aims to identify blood coagulation diagnostic biomarkers and immune changes related to SCI and its severity levels. METHODS: Human blood sequencing datasets were obtained from public databases. Differentially expressed coagulation-related genes were analyzed (DECRGs). Enrichment analysis and assessment of immune changes were conducted. Weighted gene co-expression network analysis, least absolute shrinkage and selection operator logistic regression were used to identify biomarkers. Validation for these biomarkers was performed. The correlation between biomarkers and immune cells was evaluated. Transcription factors, miRNA, lncRNA, and drugs that can regulate biomarkers were analyzed. RESULTS: DECRGs associated with SCI and its different grades were identified, showing enrichment in altered coagulation and immune-related signaling pathways. ADAM9, CD55, and STAT4 were identified as coagulation diagnostic biomarkers for SCI. IRF4 and PABPC4 were identified as coagulation diagnostic biomarkers for American Spinal Injury Association Impairment Scale (AIS) A grade of SCI. GP9 was designated as a diagnostic biomarker for AIS D grade of SCI. Immune changes in blood of SCI and its different grades were observed. Correlation between diagnostic biomarkers and immune cells were identified. Transcription factors, miRNA, lncRNA, and drugs that can regulate diagnostic biomarker expression were discovered. CONCLUSION: Therefore, detecting the expression of these putative diagnostic biomarkers and related immune changes may be helpful for predicting the severity of SCI. Uncovering potential regulatory mechanisms for biomarkers may be beneficial for further research.

A prediction model for prognosis of nephrotic syndrome with tuberculosis in intensive care unit patients: a nomogram based on the MIMIC-IV v2.2 database.

Background: Currently, a scarcity of prognostic research exists that concentrates on patients with nephrotic syndrome (NS) who also have tuberculosis. The purpose of this study was to assess the in-hospital mortality status of NS patients with tuberculosis, identify crucial risk factors, and create a sturdy prognostic prediction model that can improve disease evaluation and guide clinical decision-making. Methods: We utilized the Medical Information Mart for Intensive Care IV version 2.2 (MIMIC-IV v2.2) database to include 1,063 patients with NS complicated by TB infection. Confounding factors included demographics, vital signs, laboratory indicators, and comorbidities. The Least Absolute Shrinkage and Selection Operator (LASSO) regression and the diagnostic experiment the receiver operating characteristic (ROC) curve analyses were used to select determinant variables. A nomogram was established by using a logistic regression model. The performance of the nomogram was tested and validated using the concordance index (C-index) of the ROC curve, calibration curves, internal cross-validation, and clinical decision curve analysis. Results: The cumulative in-hospital mortality rate for patients with NS and TB was 18.7%. A nomogram was created to predict in-hospital mortality, utilizing Alb, Bun, INR, HR, Abp, Resp., Glu, CVD, Sepsis-3, and AKI stage 7 days. The area under the curve of the receiver operating characteristic evaluation was 0.847 (0.812-0.881), with a calibration curve slope of 1.00 (0.83-1.17) and a mean absolute error of 0.013. The cross-validated C-index was 0.860. The decision curves indicated that the patients benefited from this model when the risk threshold was 0.1 and 0.81. Conclusion: Our clinical prediction model nomogram demonstrated a good predictive ability for in-hospital mortality among patients with NS combined with TB. Therefore, it can aid clinicians in assessing the condition, judging prognosis, and making clinical decisions for such patients.

A New Strategy for the Design of Triple-Phase Eutectic High-Entropy Alloys Based on Infinite Solid Solution and Pseudo-Ternary Method.

Eutectic high-entropy alloys (EHEAs) have combined both high-entropy alloys and eutectic alloy contributions, with excellent castability and high-temperature application potential. Yet, multielement/triple-phase eutectic high-entropy alloy (TEHEA) designs remain puzzling. This work proposed a new strategy based on an infinite solid solution and pseudo-ternary model to reveal the puzzle of TEHEAs. The designed triple-phase eutectic high-entropy alloys (TEHEAs) with more than seven elements were identified as face-centered cubic (FCC), ordered body-centered cubic (B2), and Laves phase structures. In this work, the alloy C showcases outstanding comprehensive mechanical properties, offering a novel avenue for the design of high-performance EHEAs.

Energy- and Angle-Resolved Scattering of Ne from Dodecane Liquid Surfaces: Theory Corroborating Experiment.

Motivated by recent experimental work by the Neumark group, we present here an all-atom molecular dynamics study of Ne scattering from a dodecane liquid surface with the objective of elucidating the fundamental aspects of gas-liquid dynamics. Using a fine-tuned force field, the GPU-accelerated simulations reproduced semiquantitatively the energy- and angle-resolved experimental results. The branching ratio between the impulsive scattering (IS) and thermal desorption (TD) channels exhibits a clear correlation with the incidence energy (Ei) and angle. Ne atoms with lower Ei values are more likely to be trapped, yielding an increased TD ratio. For a given Ei, a large incidence angle led to a higher IS ratio. The energy transfer between Ne atoms and liquid dodecane was found to be more sensitive to the deflection angle than to the incidence or reflection angle. With an increasing deflection angle, the fractional energy loss increases, suggesting that more kinetic energy is transferred to the liquid.

Osr2 functions as a biomechanical checkpoint to aggravate CD8+ T cell exhaustion in tumor.

Alterations in extracellular matrix (ECM) architecture and stiffness represent hallmarks of cancer. Whether the biomechanical property of ECM impacts the functionality of tumor-reactive CD8+ T cells remains largely unknown. Here, we reveal that the transcription factor (TF) Osr2 integrates biomechanical signaling and facilitates the terminal exhaustion of tumor-reactive CD8+ T cells. Osr2 expression is selectively induced in the terminally exhausted tumor-specific CD8+ T cell subset by coupled T cell receptor (TCR) signaling and biomechanical stress mediated by the Piezo1/calcium/CREB axis. Consistently, depletion of Osr2 alleviates the exhaustion of tumor-specific CD8+ T cells or CAR-T cells, whereas forced Osr2 expression aggravates their exhaustion in solid tumor models. Mechanistically, Osr2 recruits HDAC3 to rewire the epigenetic program for suppressing cytotoxic gene expression and promoting CD8+ T cell exhaustion. Thus, our results unravel Osr2 functions as a biomechanical checkpoint to exacerbate CD8+ T cell exhaustion and could be targeted to potentiate cancer immunotherapy.

A causal examination of the correlation between hormonal and reproductive factors and low back pain.

Background: The relationship between hormonal fluctuations in the reproductive system and the occurrence of low back pain (LBP) has been widely observed. However, the causal impact of specific variables that may be indicative of hormonal and reproductive factors, such as age at menopause (ANM), age at menarche (AAM), length of menstrual cycle (LMC), age at first birth (AFB), age at last live birth (ALB) and age first had sexual intercourse (AFS) on low back pain remains unclear. Methods: This study employed Bidirectional Mendelian randomization (MR) using publicly available summary statistics from Genome Wide Association Studies (GWAS) and FinnGen Consortium to investigate the causal links between hormonal and reproductive factors on LBP. Various MR methodologies, including inverse-variance weighted (IVW), MR-Egger regression, and weighted median, were utilized. Sensitivity analysis was conducted to ensure the robustness and validity of the findings. Subsequently, Multivariate Mendelian randomization (MVMR) was employed to assess the direct causal impact of reproductive and hormone factors on the risk of LBP. Results: After implementing the Bonferroni correction and conducting rigorous quality control, the results from MR indicated a noteworthy association between a decreased risk of LBP and AAM (OR=0.784, 95% CI: 0.689-0.891; p=3.53E-04), AFB (OR=0.558, 95% CI: 0.436-0.715; p=8.97E-06), ALB (OR=0.396, 95% CI: 0.226-0.692; p=0.002), and AFS (OR=0.602, 95% CI: 0.518-0.700; p=3.47E-10). Moreover, in the reverse MR analysis, we observed no significant causal effects of LBP on ANM, AAM, LMC and AFS. MVMR analysis demonstrated the continued significance of the causal effect of AFB on LBP after adjusting for BMI. Conclusion: Our study explored the causal relationship between ANM, AAM, LMC, AFB, AFS, ALB and the prevalence of LBP. We found that early menarche, early age at first birth, early age at last live birth and early age first had sexual intercourse may decrease the risk of LBP. These insights enhance our understanding of LBP risk factors, offering valuable guidance for screening, prevention, and treatment strategies for at-risk women.

Sulfadiazine proliferated antibiotic resistance genes in the phycosphere of Chlorella pyrenoidosa: Insights from bacterial communities and microalgal metabolites.

The phycosphere is an essential ecological niche for the proliferation of antibiotic resistance genes (ARGs). However, how ARGs' potential hosts change and the driving mechanism of metabolites under antibiotic stress in the phycosphere have seldom been researched. We investigated the response of Chlorella pyrenoidosa and the structure and abundance of free-living (FL) and particle-attached (PA) bacteria, ARGs, and metabolites under sulfadiazine by using real-time quantitative PCR, 16 S rRNA high-throughput. The linkage of key bacterial communities, ARGs, and metabolites through correlations was established. Through analysis of physiological indicators, Chlorella pyrenoidosa displayed a pattern of "low-dose promotion and high-dose inhibition" under antibiotic stress. ARGs were enriched in the PA treatment groups by 117 %. At the phylum level, Proteobacteria, Bacteroidetes, and Actinobacteria as potential hosts for ARGs. At the genus level, potential hosts included Sphingopyxis, SM1A02, Aquimonas, Vitellibacter, and Proteiniphilum. Middle and high antibiotic concentrations induced the secretion of metabolites closely related to potential hosts by algae, such as phytosphingosine, Lysophosphatidylcholine, and α-Linolenic acid. Therefore, changes in bacterial communities indirectly influenced the distribution of ARGs through alterations in metabolic products. These findings offer essential details about the mechanisms behind the spread and proliferation of ARGs in the phycosphere.

The diversity of inhibitory receptor co-expression patterns of exhausted CD8+ T cells in oropharyngeal carcinoma.

Exhausted CD8+ T cells (Texs) are characterized by the expression of various inhibitory receptors (IRs), whereas the functional attributes of these co-expressed IRs remain limited. Here, we systematically characterized the diversity of IR co-expression patterns in Texs from both human oropharyngeal squamous cell carcinoma (OPSCC) tissues and syngeneic OPSCC model. Nearly 60% of the Texs population co-expressed two or more IRs, and the number of co-expressed IRs was positively associated with superior exhaustion and cytotoxicity phenotypes. In OPSCC patients, programmed cell death-1 (PD-1) blockade significantly enhanced PDCD1-based co-expression with other IR genes, whereas dual blockades of PD-1 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) significantly upregulated CTLA4-based co-expression with other IR genes. Collectively, our findings demonstrate that highly diverse IR co-expression is a leading feature of Texs and represents their functional states, which might provide essential clues for the rational selection of immune checkpoint inhibitors in treating OPSCC.

Prognostic effects of different treatment modalities for hypopharyngeal squamous cell carcinoma: Experience of two tertiary hospitals in Southwestern China.

Background: The prognostic effects of different treatment modalities on patients with hypopharyngeal squamous cell carcinoma (HPSCC) remain unclear. Methods: HPSCC patients diagnosed and treated at either West China Hospital or Sichuan Cancer Hospital between January 1, 2009, and December 31, 2019, were enrolled in this retrospective, real-world study. Survival rates were presented using Kaplan-Meier curves and compared using log-rank tests. Univariable and multivariable Cox proportional hazards regression models were used to identify the predictors of overall survival (OS). Subgroup analyses were conducted for patients with advanced-stage HPSCC (stages III and IV and category T4). Results: A total of 527 patients with HPSCC were included. Patients receiving SRC (surgery, radiotherapy [RT], and chemotherapy) showed the best OS (p < 0.0001). In comparison with RT alone, both surgery alone (all cases: hazard ratio [HR] = 0.39, p = 0.0018; stage IV cases: HR = 0.38, p = 0.0085) and surgery-based multimodality treatment (SBMT; all cases: HR = 0.27, p < 0.0001; stage IV cases: HR = 0.30, p = 0.00025) showed prognostic benefits, while SBMT also showed survival priority over chemoradiotherapy (CRT; all cases: HR = 0.52, p < 0.0001; stage IV cases: HR = 0.59, p = 0.0033). Moreover, patients who underwent surgery alone had comparable OS to those who underwent SBMT (all patients: p = 0.13; stage IV cases: p = 0.34), while CRT yielded similar prognostic outcomes as RT alone (all patients: p = 0.054; stage IV cases: p = 0.11). Conclusions: Surgery alone was comparable to SBMT and superior to RT/CRT in terms of OS in patients with HPSCC. We suggest that surgery should be encouraged for the treatment of HPSCC, even in patients with advanced-stage disease.