SUSD2 suppresses CD8+ T cell antitumor immunity by targeting IL-2 receptor signaling.

Dysfunctional CD8+ T cells, which have defective production of antitumor effectors, represent a major mediator of immunosuppression in the tumor microenvironment. Here, we show that SUSD2 is a negative regulator of CD8+ T cell antitumor function. Susd2-/- effector CD8+ T cells showed enhanced production of antitumor molecules, which consequently blunted tumor growth in multiple syngeneic mouse tumor models. Through a quantitative mass spectrometry assay, we found that SUSD2 interacted with interleukin (IL)-2 receptor α through sushi domain-dependent protein interactions and that this interaction suppressed the binding of IL-2, an essential cytokine for the effector functions of CD8+ T cells, to IL-2 receptor α. SUSD2 was not expressed on regulatory CD4+ T cells and did not affect the inhibitory function of these cells. Adoptive transfer of Susd2-/- chimeric antigen receptor T cells induced a robust antitumor response in mice, highlighting the potential of SUSD2 as an immunotherapy target for cancer.

Mitochondrial calcium uniporter promotes phagocytosis-dependent activation of the NLRP3 inflammasome.

Mitochondria, a highly metabolically active organelle, have been shown to play an essential role in regulating innate immune function. Mitochondrial Ca2+ uptake via the mitochondrial Ca2+ uniporter (MCU) is an essential process regulating mitochondrial metabolism by targeting key enzymes involved in the tricarboxylic acid cycle (TCA). Accumulative evidence suggests MCU-dependent mitochondrial Ca2+ signaling may bridge the metabolic reprogramming and regulation of immune cell function. However, the mechanism by which MCU regulates inflammation and its related disease remains elusive. Here we report a critical role of MCU in promoting phagocytosis-dependent activation of NLRP3 (nucleotide-binding domain, leucine-rich repeat containing family, pyrin domain-containing 3) inflammasome by inhibiting phagolysosomal membrane repair. Myeloid deletion of MCU (McuΔmye) resulted in an attenuated phagolysosomal rupture, leading to decreased caspase-1 cleavage and interleukin (IL)-1ß release, in response to silica or alum challenge. In contrast, other inflammasome agonists such as adenosine triphosphate (ATP), nigericin, poly(dA:dT), and flagellin induced normal IL-1ß release in McuΔmye macrophages. Mechanistically, we demonstrated that decreased NLRP3 inflammasome activation in McuΔmye macrophages was caused by improved phagolysosomal membrane repair mediated by ESCRT (endosomal sorting complex required for transport)-III complex. Furthermore, McuΔmye mice showed a pronounced decrease in immune cell recruitment and IL-1ß production in alum-induced peritonitis, a typical IL-1-dependent inflammation model. In sum, our results identify a function of MCU in promoting phagocytosis-dependent NLRP3 inflammatory response via an ESCRT-mediated phagolysosomal membrane repair mechanism.

Based on PI-RADS v2.1 combining PHI and ADC values to guide prostate biopsy in patients with PSA 4-20 ng/mL.

PURPOSE: The study aimed to investigate the diagnostic accuracy of prostate health index (PHI) and apparent diffusion coefficient (ADC) values in predicting prostate cancer (PCa) and construct a nomogram for the prediction of PCa and clinically significant PCa (CSPCa) in Prostate Imaging-Reporting and Data System (PI-RADS) three lesions cohort. METHODS: This study prospectively enrolled 301 patients who underwent multiparametric magnetic resonance (mpMRI) and were scheduled for prostate biopsy. The receiver operating characteristic curve (ROC) was performed to estimate the diagnostic accuracy of each predictor. Univariable and multivariable logistic regression analysis was conducted to ascertain hidden risk factors and constructed nomograms in PI-RADS three lesions cohort. RESULTS: In the whole cohort, the area under the ROC curve (AUC) of PHI is relatively high, which is 0.779. As radiographic parameters, the AUC of PI-RADS and ADC values was 0.702 and 0.756, respectively. The utilization of PHI and ADC values either individually or in combination significantly improved the diagnostic accuracy of the basic model. In PI-RADS three lesions cohort, the AUC for PCa was 0.817 in the training cohort and 0.904 in the validation cohort. The AUC for CSPCa was 0.856 in the training cohort and 0.871 in the validation cohort. When applying the nomogram for predicting PCa, 50.0% of biopsies could be saved, supplemented by 6.9% of CSPCa being missed. CONCLUSION: PHI and ADC values can be used as predictors of CSPCa. The nomogram included PHI, ADC values and other clinical predictors demonstrated an enhanced capability in detecting PCa and CSPCa within PI-RADS three lesions cohort.

Association between Homologous Recombination Repair Defect Status and Long-Term Prognosis of Early HER2-Low Breast Cancer: A Retrospective Cohort Study.

BACKGROUND: As a newly identified subtype of HER2-negative tumors associated with a less favorable prognosis, it remains crucial to evaluate potential prognostic and predictive factors, particularly non-invasive biomarkers, for individuals with human epidermal growth factor 2 (HER2) low early-stage breast cancer (EBC). Multiple investigations have highlighted that HER2-negative patients with EBC exhibiting high homologous recombination deficiency (HRD) scores display lower rates of pathological complete response (PCR) to neoadjuvant chemotherapy (NAC). Nevertheless, no study to date has explored the correlation between HRD and the long-term prognosis in HER2-low patients with EBC. PATIENTS AND METHODS: This retrospective observational study focuses on primary EBC sourced from The Cancer Genome Atlas dataset (TCGA). It reveals the gene mutation landscape in EBC with low HER2 expression and elucidates the tumor immune landscape across different HRD states. Utilizing bioinformatics analysis and Cox proportional models, along with the Kaplan-Meier method, the study assesses the correlation between HRD status and disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). Subgroup analyses were conducted to identify potential variations in the association between HRD and prognosis. RESULTS: In the patients with HER2-low breast cancer, patients with homologous recombination related genes (HRRGs) defects had an HRD score about twice that of those without related genes mutations, and were at higher risk of acquiring ARID1A, ATM, and BRCA2 mutations. We also found that most immune cell abundances were significantly higher in EBC tumors with high HRD than in EBC tumors with low HRD or HRD-medium, particularly plasma B-cell abundance, CD8 T-cell abundance, and M1 macrophages. In addition, these tumors with HRD-high also appear to have significantly higher tumor immune scores and lower interstitial scores. Then, we analyzed the relationship between different HRD status and prognosis. There was statistical significance (P = .036 and P = .046, respectively) in DSS and PFI between the HRD-low and HRD-high groups, and patients with HRD-high EBC showed relatively poor survival outcomes. A medium HRD score (hazard ratio, HR = 2.15, 95% CI: 1.04-4.41, P = .038) was a significant risk factor for PFI. Hormone receptor positivity is an important factor in obtaining medium-high HRD score and poor prognosis. CONCLUSION: Higher HRD scores were associated with poorer PFI outcomes, particularly in people with HR+/HER2-low. Varied HRD states exhibited distinctions in HRRGs and the tumor immune landscape. These insights have the potential to assist clinicians in promptly identifying high-risk groups and tailoring personalized treatments for patients with HER2-low EBC, aiming to enhance long-term outcomes.

Highly Stable Solid Contact Calcium Ion-Selective Electrodes: Rapid Ion-Electron Transduction Triggered by Lipophilic Anions Participating in Redox Reactions of CunS Nanoflowers.

Solid contact (SC) calcium ion-selective electrodes (Ca2+-ISEs) have been widely applied in the analysis of water quality and body fluids by virtue of the unique advantages of easy operation and rapid response. However, the potential drift during the long-term stability test hinders their further practical applications. Designing novel redox SC layers with large capacitance and high hydrophobicity is a promising approach to stabilize the potential stability, meanwhile, exploring the transduction mechanism is also of great guiding significance for the precise design of SC layer materials. Herein, flower-like copper sulfide (CunS-50) composed of nanosheets is meticulously designed as the redox SC layer by modification with the surfactant (CTAB). The CunS-50-based Ca2+-ISE (CunS-50/Ca2+-ISE) demonstrates a near-Nernstian slope of 28.23 mV/dec for Ca2+ in a wide activity linear range of 10-7 to 10-1 M, with a low detection limit of 3.16 × 10-8 M. CunS-50/Ca2+-ISE possesses an extremely low potential drift of only 1.23 ± 0.13 µV/h in the long-term potential stability test. Notably, X-ray absorption fine-structure (XAFS) spectra and electrochemical experiments are adopted to elucidate the transduction mechanism that the lipophilic anion (TFPB-) participates in the redox reaction of CunS-50 at the solid-solid interface of ion-selective membrane (ISM) and redox inorganic SC layer (CunS-50), thereby promoting the generation of free electrons to accelerate ion-electron transduction. This work provides an in-depth comprehension of the transduction mechanism of the potentiometric response and an effective strategy for designing redox materials of ion-electron transduction triggered by lipophilic anions.

SPINK5 inhibits esophageal squamous cell carcinoma metastasis via immune activity.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a predominant subtype of esophageal cancer with relatively high mortality worldwide. Serine peptidase inhibitor Kazal-type 5 (SPINK5) is reported to be downregulated in ESCC. However, its explicit role in ESCC remains further investigation. METHODS: The tumor tissues and adjacent non-cancerous tissues were obtained from 196 patients with ESCC for the determination of SPINK5 mRNA levels. Additionally, the relationship between SPINK5 mRNA levels and clinicopathological features of ESCC patients was explored. The effects of SPINK5 on the invasion and migration of ESCC cells were assessed using Transwell assays. Furthermore, SPINK5 mRNA and LEKTI protein were measured in ESCC cell lines after treatment with poly (I:C), lipopolysaccharide (LPS) or unmethylated CpG DNA. Moreover, the correlation between expression of SPINK5 and nuclear factor-kappa B (NF-κB) signaling pathway-related genes was analyzed in the TCGA-ESCC cohort, and the effects of SPINK5 on NF-κB transcription was analyzed using a luciferase reporter gene assay. Finally, the correlations between SPINK5 and infiltration of immune cells, immune scores, stromal scores and ESTIMATE (i.e., Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) scores were explored. RESULTS: SPINK5 mRNA levels were downregulated in tumor tissues, which was significantly correlated with higher lymph node metastases. Overexpressed SPINK5 inhibited cell invasion and migration in ESCC cell lines. Mechanistically, LPS-induced activation of Toll-like receptor 4 (TLR4) decreased SPINK5 mRNA and LEKTI in KYSE150 and KYSE70 cells. Spearman correlation analysis revealed that SPINK5 mRNA was significantly negatively correlated with a total of seven NF-κB signaling pathway-related genes in TCGA-ESCC patients. Moreover, downregulation of SPINK5 increased and upregulation of SPINK5 decreased the activity of the NF-κB promoter in HEK293T cells. Finally, immune cells infiltration analysis revealed that SPINK5 was significantly correlated with the infiltration of various immune cells, stromal scores, immune scores and ESTIMATE scores. CONCLUSIONS: SPINK5 plays critical roles in the TLR4/NF-κB pathway and immune cells infiltration, which might contribute to the ESCC metastasis. The findings of the present study may provide a promising biomarker for the diagnosis and treatment of esophageal squamous cell carcinoma.

Formulating N-Doped Carbon Hollow Nanospheres with Highly Accessible Through-Pores to Isolate Fe Single-Atoms for Efficient Oxygen Reduction.

It is challenging yet promising to design highly accessible N-doped carbon skeletons to fully expose the active sites inside single-atom catalysts. Herein, mesoporous N-doped carbon hollow spheres with regulatable through-pore size can be formulated by a simple sequential synthesis procedure, in which the condensed SiO2 is acted as removable dual-templates to produce both hollow interiors and through-pores, meanwhile, the co-condensed polydopamine shell is served as N-doped carbon precursor. After that, Fe─N─C hollow spheres (HSs) with highly accessible active sites can be obtained after rationally implanting Fe single-atoms. Microstructural analysis and X-ray absorption fine structure analysis reveal that high-density Fe─N4 active sites together with tiny Fe clusters are uniformly distributed on the mesoporous carbon skeleton with abundant through-pores. Benefitted from the highly accessible Fe─N4 active sites arising from the unique through-pore architecture, the Fe─N─C HSs demonstrate excellent oxygen reduction reaction (ORR) performance in alkaline media with a half-wave potential up to 0.90 V versus RHE and remarkable stability, both exceeding the commercial Pt/C. When employing Fe─N─C HSs as the air-cathode catalysts, the assembled Zn-air batteries deliver a high peak power density of 204 mW cm-2 and stable discharging voltage plateau over 140 h.

Poor Medication Access as a Driver of Excess Heart-Failure Readmissions Among Patients Living in Economically Deprived Neighborhoods.

BACKGROUND: Patients residing in socioeconomically deprived neighborhoods experience higher hospital readmission rates after hospitalization for heart failure (HF). The role of medication access in the excessive readmissions in this group is poorly understood. This study explored patients' perspectives on medication access by individuals living in socioeconomically deprived neighborhoods who had experienced HF readmission. METHODS: We conducted semistructured in-depth interviews with 25 patients (mean age 61 ± 9 years, 96% Black, 40% women) who were readmitted with acute HF at Emory Healthcare hospitals and were living in highly deprived neighborhoods (top decile of the Social Deprivation Index). Qualitative descriptive analyses of the interviews were performed by using a multilevel coding strategy. RESULTS: Most patients (84%) highlighted medications as a driver of HF readmission. Patients' reported reasons for lack of medication access included medication costs (60%), having access to refills only through an emergency department or hospitalization (36%), limited access to transportation (12%), and limited understanding of medications' role in disease management (12%). CONCLUSION: Lack of access to medications for patients with HF who live in socioeconomically distressed neighborhoods exacerbate excess hospitalizations in this vulnerable population. This study focuses on patients' perspectives and experiences and identifies some potentially high-value areas to focus on in trying to enhance access and adherence to evidence-based therapies.

Comparison of the adherence of nontypeable haemophilus influenzae to lung epithelial cells.

OBJECTIVE: Nontypeable Haemophilus influenzae (NTHi) plays an important role in respiratory tract infections, and adherence to lung epithelial cells is the first step in lung infections. To explore the role of NTHi in childhood lung infections, a comparative study was conducted on the adherence of strains isolated from sputum culture and bronchoalveolar lavage fluid to A549 lung epithelial cells. METHODS: Haemophilus influenzae strains were obtained from the sample bank of Shenzhen Children's Hospital, and identified as NTHi via PCR detection of the capsule gene bexA. NTHi obtained from healthy children's nasopharyngeal swabs culture were selected as the control group, and a comparative study was conducted on the adherence of strains isolated from sputum culture or bronchoalveolar lavage fluid of patients to A549 cells. RESULTS: The adherence bacterial counts of NTHi isolated from the nasopharyngeal cultures of healthy children to A549 cells was 58.2 CFU. In patients with lung diseases, NTHi isolated from bronchoalveolar lavage fluid was 104.3 CFU, and from sputum cultures was 115.1 CFU, both of which were significantly higher in their adherence to A549 cells compared to the strains isolated from the healthy control group. There was no significant difference in adherence between the strains isolated from sputum cultures and bronchoalveolar lavage fluid (t = 0.5217, p = 0.6033). CONCLUSION: NTHi played an important role in childhood pulmonary infections by enhancing its adherence to lung epithelial cells.

Association between drinking water sources and cognitive functioning in Chinese older adults residing in rural areas.

OBJECTIVES: To explore the association between drinking water sources and cognitive functioning among older adults residing in rural China. METHODS: Data were extracted from the 2008-2018 Chinese Longitudinal Healthy Longevity Survey. Drinking water sources were categorized according to whether purification measures were employed. The Chinese version of the Mini-Mental State Examination was used for cognitive functioning assessment, and the score of <24 was considered as having cognitive dysfunction. Cox regression analyses were conducted to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the effects of various drinking water sources, changes in such sources, and its interaction with exercise on cognition dysfunction. RESULTS: We included 2304 respondents aged 79.67 ± 10.02 years; of them, 1084 (44.49%) were men. Our adjusted model revealed that respondents consistently drinking tap water were 21% less likely to experience cognitive dysfunction compared with those drinking untreated water (HR = 0.79, 95% CI: 0.70-0.90). Respondents transitioning from natural to tap water showed were 33% less likely to experience cognitive dysfunction (HR = 0.67, 95% CI: 0.58-0.78). Moreover, the HR (95% CI) for the interaction between drinking tap water and exercising was 0.86 (0.75-1.00) when compared with that between drinking untreated water and not exercising. All results adjusted for age, occupation, exercise, and body mass index. CONCLUSIONS: Prolonged tap water consumption and switching from untreated water to tap water were associated with a decreased risk of cognitive dysfunction in older individuals. Additionally, exercising and drinking tap water was synergistically associated with the low incidence of cognitive dysfunction. These findings demonstrate the importance of prioritizing drinking water health in rural areas, indicating that purified tap water can enhance cognitive function among older adults.

Solid fuel use, socioeconomic status and depression: a cross-study of older adults in China.

BACKGROUND: Indoor air pollution causes severe psychological stress and promotes depression. A better understanding of the impact of solid fuel consumption and socioeconomic indicators on mental health is critical to promote successful aging. In this study, we analyzed the relationship of depression with socioeconomic status (SES) and solid fuel use, and illustrated the mediating role of solid fuel use in the relationship between SES and depression. METHODS: 9250 participants from the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey were included in this study. A logistic regression analysis was used to calculate odds ratio (OR) and 95% confidence interval (CI) of depression for different types of fuel consumption. The stepwise approach and the Sobel test were used to test the mediation effect. RESULTS: Older people who reported the consumption of solid fuels showed higher odds of having depressive symptoms (OR = 1.16, 95% CI:1.03, 1.31). In model with depression as the outcome variable, the ORs of low education level and low annual household income level were 1.30 (95% CI: 1.15, 1.47) and 1.43 (95% CI: 1.28, 1.59) respectively. Solid fuel consumption accounted for 38.40% of the effect of a low education level and 54.73% of the effect of low income on depression. CONCLUSIONS: Solid fuel use and SES are associated with depression, and solid fuel use may act as a potential mediator connecting socioeconomic indicators and depression.

Glutamine attenuates bisphenol A-induced intestinal inflammation by regulating gut microbiota and TLR4-p38/MAPK-NF-κB pathway in piglets.

Bisphenol A (BPA), as a kind of widely exerted environmental hazardous material, brings toxicity to both humans and animals. This study aimed to investigate the role of glutamine (Gln) in intestinal inflammation and microbiota in BPA-challenged piglets. Thirty-two piglets were randomly divided into four groups according to 2 factors including BPA (0 vs. 0.1%) and Gln (0 vs. 1%) supplemented in basal diet for a 42-day feeding experiment. The results showed BPA exposure impaired piglet growth, induced intestinal inflammation and disturbed microbiota balance. However, dietary Gln supplementation improved the growth performance, while decreasing serum pro-inflammatory cytokine levels in BPA-challenged piglets. In addition, Gln attenuated intestinal mucosal damage and inflammation by normalizing the activation of toll-like receptor 4 (TLR4)-p38/MAPK-nuclear factor-kappa B (NF-κB) pathway caused by BPA. Moreover, dietary Gln supplementation decreased the abundance of Actinobacteriota and Proteobacteria, and attenuated the decreased abundance of Roseburia, Prevotella, Romboutsia and Phascolarctobacterium and the content of short-chain fatty acids in cecum contents caused by BPA exposure. Moreover, there exerted potential relevance between the gut microbiota and pro-inflammatory cytokines and cecal short-chain fatty acids. In conclusion, Gln is critical nutrition for attenuating BPA-induced intestinal inflammation, which is partially mediated by regulating microbial balance and suppressing the TLR4/p38 MAPK/NF-κB signaling.

Rotavirus genotypes in the post-vaccine era: A systematic review and meta-analysis of global, regional, and temporal trends in settings with and without rotavirus vaccine introduction.

BACKGROUND: Even moderate differences in rotavirus vaccine effectiveness against non-vaccine genotypes may exert selective pressures on circulating rotaviruses. Whether this vaccine effect or natural temporal fluctuations underlie observed changes in genotype distributions is unclear. METHODS: We systematically reviewed studies reporting rotavirus genotypes from children <5 years of age globally between 2005 and 2023. We compared rotavirus genotypes between vaccine-introducing and non-introducing settings globally and by World Health Organization (WHO) region, calendar time, and time since vaccine introduction. RESULTS: Crude pooling of genotype data from 361 studies indicated higher G2P[4], a non-vaccine genotype, prevalence in vaccine-introducing settings, both globally and by WHO region. This difference did not emerge when examining genotypes over time in the Americas, the only region with robust longitudinal data. Relative to non-introducing settings, G2P[4] detections were more likely in settings with recent introduction (e.g. 1-2 years post-introduction aOR: 4.39 (95% CI: 2.87-6.72)) but were similarly likely in settings with more time elapsed since introduction, (e.g. 7 or more years aOR (1.62 95% CI: 0.49-5.37)). CONCLUSIONS: When accounting for both regional and temporal trends, there was no substantial evidence of long-term vaccine-related selective pressures on circulating genotypes. Increased prevalence of G2P[4] may be transient after rotavirus vaccine introduction.

Microstructured Optical Fiber-Enhanced Light-Matter Interaction Enables Highly Sensitive Exosome-Based Liquid Biopsy of Breast Cancer.

Exosome-based liquid biopsies highlight potential utility in diagnosis and determining the prognosis of patients with cancer and other diseases. However, the existing techniques are severely limited for practical applications due to the complications of high cost, low sensitivity, tedious procedures, and large sample consumption. Herein, we report a microstructured optical fiber sensor for fast, sensitive, and accurate quantification of exosomes in blood samples of breast cancer patients. Numerical simulations are applied to demonstrate that hollow-core microstructured antiresonant fibers (HARFs) can stringently confine light in the fiber core, ensuring strong light-matter interaction and thus maximumly amplifying the signal. Taking this advantage, a AuNPs-dsDNA assembly containing gold nanoparticles, a recognizing DNA aptamer, and a fluorescent reporter DNA sequence is fabricated followed by immobilization on the fiber wall to form a AuNPs-dsDNA-HARF sensor. Cancer-derived exosomes can be recognized and captured in the fiber channel and generate dose-dependent fluorescent signals for quantification. The microfiber sensor demonstrates enhanced sensitivity and specificity, enabling the detection of single digits of exosome particles at the nanoliter sample level. In addition, by tracking exosome phenotypic changes, the proposed fiber sensor can facilitate precise drug treatment monitoring. This work provides a robust platform for exosome-based biopsy for cancer diagnosis and prediction of therapeutic outcomes.

Racial differences in low natriuretic peptide levels: Implications for heart failure clinical trials.

BACKGROUND: Some patients with heart failure (HF) have low natriuretic peptide (NP) levels. It is unclear whether specific populations are disproportionately excluded from participation in randomized clinical trials (RCT) with inclusion requirements for elevated NPs. We investigated factors associated with unexpectedly low NP levels in a cohort of patients hospitalized with HF, and the implications on racial diversity in a prototype HF RCT. METHODS: We created a retrospective cohort of 31,704 patients (age 72 ± 16 years, 49% female, 52% Black) hospitalized with HF from 2010 to 2020 with B-type natriuretic peptide (BNP) measurements. Factors associated with unexpectedly low BNP levels (<50 pg/mL) were identified using multivariable logistic regression models. We simulated patient eligibility for a prototype HF trial using specific inclusion and exclusion criteria, and varying BNP cut-offs. RESULTS: Unexpectedly low BNP levels were observed in 8.9% of the cohort. Factors associated with unexpectedly low BNP levels included HFpEF (aOR 3.76, 95% CI: 3.36, 4.20), obesity (aOR 1.96, 95% CI: 1.73, 2.21), self-identification as Black (aOR 1.53, 95% CI: 1.36, 1.71), and male gender (aOR 1.45, 95% CI: 1.31, 1.60). Applying limited clinical inclusion and exclusion criteria from PARAGLIDE-HF disproportionately excluded Black patients, with impairment in renal function having the greatest impact. Adding thresholds for BNP of ≥35, ≥50, ≥67, ≥100, and ≥150 pg/mL demonstrated the risk of exclusion was higher for Black compared to non-Black patients (RR = 2.03 [95% CI: 1.73, 2.39], 1.90 [95% CI: 1.68, 2.15], 1.63 [95% CI: 1.48, 1.81], 1.38 [95% CI: 1.28, 1.50], and 1.23 [95% CI: 1.15, 1.31], respectively). CONCLUSIONS: Nearly 10% of patients hospitalized with HF have unexpectedly low BNP levels. Simulating inclusion into a prototype HFpEF RCT demonstrated that requiring increasingly elevated NP levels disproportionately excludes Black patients.

Nitrogen fertilization modulates beneficial rhizosphere interactions through signaling effect of nitric oxide.

Chemical nitrogen (N) fertilization is customary for increasing N inputs in agroecosystems. The nutritional effects of N fertilization on plants and soil microbes have been well studied. However, the signaling effects of N fertilization on rhizosphere plant-microbe interactions and the following feedback to plant performance remain unknown. Here, we investigated the effect of different N fertilizations on the behavior of the plant growth-promoting rhizobacteria (PGPR) Bacillus velezensis SQR9 in the cucumber (Cucumis sativus L.) rhizosphere. Moderate N fertilization promoted higher rhizosphere colonization of strain SQR9 than insufficient or excessive N input. Nitric oxide (NO) produced through the denitrification process under N fertilization was identified as the signaling molecule that dominates the root colonization of PGPR, and this effect could be neutralized by the NO-specific scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxy-3-oxide. Gene expression analysis demonstrated that NO regulated the biofilm formation of strain SQR9 by affecting the synthesis of extracellular matrix γ-polyglutamic acid, consequently impacting its root colonization. Finally, we demonstrated that moderate N fertilization-modulated enhanced PGPR root colonization can significantly promote plant growth and nitrogen use efficiency. This study provides insights into our understanding of the beneficial rhizosphere plant-microbe interactions under N fertilization and suggests that rational fertilization is critical to promote beneficial rhizosphere interactions for sustainable agricultural production.

Guar Gum-Based Macroporous Hygroscopic Polymer for Efficient Atmospheric Water Harvesting.

Solar-driven atmospheric water harvesting technology has the advantage of not being limited by geography and has great potential in solving the freshwater crisis. Here, we first propose a purely natural and degradable superhydrophilic composite macroporous hygroscopic material by applying guar gum (GG) to atmospheric water harvesting. The material consists of GG-cellulose nanofibers (CNFs) as a porous substrate material, limiting the hygroscopic factor lithium chloride (LiCl) in its three-dimensional (3D) network structure, and carbon nanotubes (CNTs) play a photothermal conversion role. The composite material has a high light absorption rate of more than 95%, and the macroporous structure (20-60 µm) allows for rapid adsorption/desorption kinetics. At 35 °C and 90% relative humidity (RH), the moisture absorption capacity is as high as 1.94 g/g. Under 100 mW/cm2 irradiation, the absorbed water is almost completely desorbed within 3 h, and the water harvesting performance is stable in 10 cycles. Moreover, liquid water was successfully collected in an actual outdoor experiment. This work demonstrates the great potential of biomass materials in the field of atmospheric water collection and provides more opportunities for various energy and sustainable applications in the future.

Association of Socioeconomic Disparities With Nasopharyngeal Carcinoma Survival in an Endemic Area, China.

OBJECTIVES: This retrospective cohort study investigated the association of socioeconomic status with survival outcomes among patients with nasopharyngeal carcinoma in an endemic area of China. METHODS: The primary endpoint was overall survival. Survival outcomes were estimated by the Kaplan-Meier method and compared by the log-rank test, and the multivariate Cox proportional hazards model was used to estimate hazard ratios, 95% CIs, and independent prognostic factors. RESULTS: A total of 11 069 adult patients with NPC were enrolled and included in the analysis. Kaplan-Meier survival analysis revealed that overall survival was significantly different among socioeconomic status. Compared with high socioeconomic status patients, low socioeconomic status patients (HR, 1.190; 95% CI, 1.063-1.333) and medium socioeconomic status patients (HR, 1.111; 95% CI, 1.006-1.226) were associated with increased hazard ratio (HR) of overall survival. CONCLUSION: This analysis highlights patients with nasopharyngeal carcinoma who had high socioeconomic status had better overall survival compared with those who had low and medium socioeconomic status.

Investigating on sensing mechanism of MoS2-FET biosensors in response to proteins.

Field-effect transistor (FET) biosensors based on two-dimensional materials have gained extensive attention due to their high sensitivity, label-free detection capability, and fast response. Molybdenum disulfide (MoS2), with tunable bandgap, high surface-to-volume ratio, and smooth surface without dangling bonds, is a promising material for FET biosensors. Previous reports have demonstrated the fabrication of MoS2-FET biosensors and their high sensitivity detection of proteins. However, most prior research has focused on the realization of MoS2-FETs for detecting different kinds of proteins or molecules, while comprehensive analysis of the sensing mechanism and dominant device factors of MoS2-FETs in response to proteins is yet to investigate. In this study, we first fabricated MoS2-FET biosensor and detected different types of proteins (immunoglobulin G (IgG),ß-actin, and prostate-specific antigen (PSA)). Secondly, we built the model of the device and analyzed the sensing mechanism of MoS2-FETs in response to proteins. Experimental and modeling results showed that the induced doping effect and gating effect caused by the target protein binding to the device surface were the major influential factors. Specifically, the channel doping concentration and gate voltage (Vg) offset exhibited monotonic change as the concentration of the protein solution increases. For example, the channel doping concentration increased up to ∼37.9% and theVgoffset was ∼-1.3 V with 10-7µgµl-1IgG. The change was less affected by the device size. We also investigated the effects of proteins with opposite acid-base properties (ß-actin and PSA) to IgG on the device sensing mechanism.ß-actin and PSA exhibited behavior opposite to that of IgG. Additionally, we studied the response behavior of MoS2-FETs with different dimensions and dielectric materials (channel length, MoS2thickness, dielectric layer thickness, dielectric layer material) to proteins. The underlying mechanisms were discussed in details. This study provides valuable guidelines for the design and application of MoS2-FET biosensors.

3-Methyladenine ameliorates surgery-induced anxiety-like behaviors in aged mice by inhibiting autophagy-induced excessive oxidative stress.

BACKGROUND: Postoperative anxiety is a common surgical complication in older patients. Research has recently linked excessive autophagy to several neurological disorders, including anxiety. This study aimed to determine whether 3-Methyladenine (3-MA) administration reduced anxiety-like behaviors in a mouse model following abdominal exploratory laparotomy. METHODS: An abdominal exploratory laparotomy model of postoperative anxiety was established using male C57BL/6 mice aged 20 months. 3-MA (6, 30, and 150 mg/ml) was administered via intracerebroventricular immediately following surgery. The mice were assessed 14 days after surgery using the marble burying, elevated plus maze tests, and local field potential recording in the amygdala. The levels of expression of phosphorylated-Akt, Beclin-1, LC3B, nuclear factor erythroid 2-related factor 2 (Nrf2)-occupied regions in NeuN-positive cells, superoxide dismutase (SOD) activity, malondialdehyde (MDA), and glutathione (GSH) were measured at 24 h after surgery. RESULTS: The injection of 3-MA reversed the increased number of marbles buried, decreased time spent in the open arm, and enhanced θ oscillation power after 14 days of abdominal exploratory laparotomy. In addition, administration of 3-MA reduced the ratio of phosphorylated- to total-Akt, decreased expression in Beclin-1 and LC3B, attenuated MDA levels, and increased the ratio of Nrf2-occupied areas in NeuN-positive cells, SOD activity, and GSH levels under abdominal exploratory laparotomy conditions. CONCLUSIONS: 3-MA improved anxiety-like behaviors in aged mice undergoing abdominal exploratory laparotomy by inhibiting excessive autophagy-induced oxidative stress. These results suggest that 3-MA could be an effective treatment for postoperative anxiety.