Early surveillance of rice bakanae disease using deep learning and hyperspectral imaging.

Bakanae disease, caused by Fusarium fujikuroi, poses a significant threat to rice production and has been observed in most rice-growing regions. The disease symptoms caused by different pathogens may vary, including elongated and weak stems, slender and yellow leaves, and dwarfism, as example. Bakanae disease is likely to cause necrosis of diseased seedlings, and it may cause a large area of infection in the field through the transmission of conidia. Therefore, early disease surveillance plays a crucial role in securing rice production. Traditional monitoring methods are both time-consuming and labor-intensive and cannot be broadly applied. In this study, a combination of hyperspectral imaging technology and deep learning algorithms were used to achieve in situ detection of rice seedlings infected with bakanae disease. Phenotypic data were obtained on the 9th, 15th, and 21st day after rice infection to explore the physiological and biochemical performance, which helps to deepen the research on the disease mechanism. Hyperspectral data were obtained over these same periods of infection, and a deep learning model, named Rice Bakanae Disease-Visual Geometry Group (RBD-VGG), was established by leveraging hyperspectral imaging technology and deep learning algorithms. Based on this model, an average accuracy of 92.2% was achieved on the 21st day of infection. It also achieved an accuracy of 79.4% as early as the 9th day. Universal characteristic wavelengths were extracted to increase the feasibility of using portable spectral equipment for field surveillance. Collectively, the model offers an efficient and non-destructive surveillance methodology for monitoring bakanae disease, thereby providing an efficient avenue for disease prevention and control. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00169-1.

Autophagy in Oligodendrocyte Lineage Cells Controls Oligodendrocyte Numbers and Myelin Integrity in an Age-dependent Manner.

Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.

Value of Glycemic Dispersion Index in Predicting Major Adverse Cardiovascular Events in Diabetic Patients with Concomitant Acute Coronary Syndrome.

Aim: This investigation aims to assess the predictive value of the glycemic dispersion index (GDI), calculated by incorporating glycated hemoglobin, fasting plasma glucose, and 2-hour postprandial plasma glucose, in predicting major adverse cardiovascular events (MACE) within a 12-month timeframe for diabetic patients with concomitant acute coronary syndrome (ACS). Methods: A retrospective study was conducted on 3261 diabetic patients with ACS who were hospitalized in the Department of Cardiology, the Sixth Affiliated Hospital of Kunming Medical University, from January 2016 to July 2022. Based on the inclusion and exclusion criteria, 512 patients were ultimately enrolled in the study. Their general information and laboratory test indicators were collected, and the occurrence of MACE within 12 months after admission was followed up and recorded for the enrolled patients, With the last follow-up having been concluded on July 31, 2023. The enrolled patients were stratified into four groups (Q1, Q2, Q3, Q4) based on their GDI values, from the lowest to the highest. Cox proportional hazards regression analysis and Kaplan-Meier survival analysis were employed to investigate the risk factors associated with MACE occurrence across these groups and to assess the cumulative risk of MACE over time within each group. Results: The percentages of enrolled patients experiencing MACE in groups Q1 to Q4 were 10.16%, 12.50%, 15.63%, and 16.41%, respectively. GDI independently predicted the hazards for MACE in enrolled patients. The cumulative risk of MACE over time was considerably more significant in those with a GDI>4.21 than those with a GDI≤4.21. Conclusion: The elevated GDI is correlated with an augmented risk of MACE in diabetic patients with concomitant ACS, thereby serving as an early indicator for assessing the unfavorable clinical prognosis of patients. This study offers novel insights into glycemic variability monitoring, enhancing prevention and treatment strategies for cardiovascular disease in people with diabetes.

Global school plate waste estimates highlight the need for building a sustainable food education system.

Food waste reduction is essential for supporting the sustainability of food systems. Wasteful behaviours are difficult to change after they have been formed, highlighting the importance of early interventions. Here we present an assessment of school plate food waste from 29 countries, and examine the environmental implications, causes, and interventions. School plate waste ranged from 4% to 46% per capita per meal and was positively correlated with country income levels. On a global scale, this waste embodies ∼150 Mha of cropland and ∼770 MtCO2e of greenhouse gas emissions; hence, reducing school plate food waste offers potentially large environmental gains. We propose a comprehensive, multistakeholder framework centred around sustainable food education that cultivates food systems knowledge and skills, and an appreciation for nature and food labour to reduce the psychological distance between youth and their food waste. To effectively implement the framework requires the support and engagement of families, communities and the broader society beyond the confines of schools.

Microstructural and functional substrates underlying dispositional greed and its link with trait but not state impulsivity.

The interplay between personality traits and impulsivity has long been a central theme in psychology and psychiatry. However, the potential association between Greed Personality Traits (GPT) and impulsivity, encompassing both trait and state impulsivity and future time perspective, remains largely unexplored. To address these issues, we employed questionnaires and an inter-temporal choice task to estimate corresponding trait/state impulsivity and collected multi-modal neuroimaging data (resting-state functional imaging: n = 430; diffusion-weighted imaging: n = 426; task-related functional imaging: n = 53) to investigate the underlying microstructural and functional substrates. Behavioral analyses revealed that GPT mediated the association between time perspective (e.g., present fatalism) and trait impulsivity (e.g., motor impulsivity). Functional imaging analyses further identified that brain activation strengths and patterns related to delay length, particularly in the dorsomedial prefrontal cortex, superior parietal lobule, and cerebellum, were associated with GPT. Moreover, individuals with similar levels of greed exhibited analogous spontaneous brain activity patterns, predominantly in the Default Mode Network (DMN), Fronto-Parietal Network (FPN), and Visual Network (VIS). Diffusion imaging analysis observed specific microstructural characteristics in the spinocerebellar/pontocerebellar fasciculus, internal/external capsule, and corona radiata that support the formation of GPT. Furthermore, the corresponding neural activation pattern, spontaneous neural activity pattern, and analogous functional couplings among the aforementioned brain regions mediated the relationships between time perspective and GPT and between GPT and motor impulsivity. These findings provide novel insights into the possible pathway such as time perspective → dispositional greed → impulsivity and uncover their underlying microstructural and functional substrates.

Structural characterization of polysaccharides from Panax ginseng C. A. Meyer root and their triggered potential immunoregulatory and radioprotective activities.

With people's increasing awareness of healthy diet, the diverse health-promoting functions of ginseng have been widely recognized. As one of the key functional components, ginseng polysaccharides have attracted increasing research interest. Here, three purified polysaccharide fractions, GPS-1a, GPS-1b, and GPS-2, were obtained from the root extract of Panax ginseng C. A. Meyer. Structurally, GPS-1a and GPS-1b were both linked in a â†’ 6)-α-D-Glcp-(1 â†’ pattern but composed of glucose and galactose in molar ratios of 9.76:0.24 and 9.81:0.19. In contrast, GPS-2 was composed of glucose, galactose, arabinose, rhamnose, and galacturonic acid in a molar ratio of 1.82:1.94:0.79:0.52:4.93. The main backbone consisted of →4)-α-D-GalpA-(1→, →4)-α-D-GalpA-6OMe-(1→, →3, 4)-α-D-GalpA-(1→, →3)-α-L-Rhap-(1 â†’ linages, and its branches are composed of →5)-α-L-Araf-(1→, →4)-ß-D-Galp-(1→, →2)-ß-D-Glcp-(1→, α-D-GalAp-(1→. Benefitting from this structural variance, GPS-2 exhibited the most significant immunoregulatory and radioprotective efficacies. Specifically, GPS-2 promoted TLR2, NF-κB, and TRAF6 protein expression levels, thereby significantly improving macrophage phagocytosis, splenic lymphocyte proliferation, and stimulation of NO, IL-1ß, IL-6, and TNF-α secretion, which activated RAW264.7 and splenic lymphocytes. The following radioprotection activity tests unveiled that GPS-2 increased the organ index, number of peripheral blood cells, cellularity of splenocytes, and bone marrow cell numbers in irradiated mice. This investigation revealed the contribution of polysaccharide structure characteristics to the bioactive expression and elucidated the potential utilization of GPS-2 as a radioprotective agent or immunomodulator.

Biomolecular condensation of ERC1 recruits ATG8 and NBR1 to drive autophagosome formation for plant heat tolerance.

Macroautophagy (hereafter autophagy) is essential for cells to respond to nutrient stress by delivering cytosolic contents to vacuoles for degradation via the formation of a multi-layer vesicle named autophagosome. A set of autophagy-related (ATG) regulators are recruited to the phagophore assembly site for the initiation of phagophore, as well as its expansion and closure and subsequent delivery into the vacuole. However, it remains elusive that how the phagophore assembly is regulated under different stress conditions. Here, we described an unknown Arabidopsis (Arabidopsis thaliana) cytosolic ATG8-interaction protein family (ERC1/2), that binds ATG8 and NBR1 to promote autophagy. ERC1 proteins translocate to the phagophore membrane and develop into classical ring-like autophagosomes upon autophagic induction. However, ERC1 proteins form large droplets together with ATG8e proteins when in the absence of ATG8 lipidation activity. We described the property of these structures as phase-separated membraneless condensates by solving the in vivo organization with spatial and temporal resolution. Moreover, ERC1 condensates elicits a strong recruitment of the autophagic receptor NBR1. Loss of ERC1 suppressed NBR1 turnover and attenuated plant tolerance to heat stress condition. This work provides novel insights into the mechanical principle of phagophore initiation via an unreported ERC1-mediated biomolecular condensation for heat tolerance in Arabidopsis .

Inhibiting H2AX Can Ameliorate Myocardial Ischemia/Reperfusion Injury by Regulating P53/JNK Signaling Pathway.

Myocardial ischemia-reperfusion (I/R) injury is a significant area of focus in cardiovascular disease research. I/R injury can increase intracellular oxidative stress, leading to DNA damage. H2AX plays a crucial role in DNA repair. This study utilized mouse and cell models of myocardial I/R to investigate the impact of H2AX on cardiomyocytes during I/R. This study initially assessed the expression of H2AX in MI/R mice compared to a sham surgery group. Subsequently, cardiac function, infarct area, and mitochondrial damage were evaluated after inhibiting H2AX in MI/R mice and a negative control group. Furthermore, the study delved into the molecular mechanisms by analyzing the expression of H2AX, P53, p-JNK, SHP2, p-SHP2, p-RAS, parkin, Drp1, Cyt-C, Caspase-3, and Caspase-8 in cardiomyocytes following the addition of JNK or P53 agonists. The results from western blotting in vivo indicated significantly higher H2AX expression in the MI/R group compared to the sham group. Inhibiting H2AX improved cardiac function, reduced myocardial infarct area, and mitigated mitochondrial damage in the MI/R group. In vitro experiments demonstrated that inhibiting H2AX could attenuate mitochondrial damage and apoptosis in myocardial cells by modulating the P53 and JNK signaling pathways. These findings suggested that inhibiting H2AX may alleviate myocardial I/R injury through the regulation of the P53/JNK pathway, highlighting H2AX as a potential target for the treatment of myocardial ischemia/reperfusion injury.

Unveiling the Interplay Between Depressive Symptoms' Alleviation and Quality of Life Improvement in Major Depressive Disorder: A Network Analysis Based on Longitudinal Data.

Background: Understanding the dynamic relationship between depressive symptoms and quality of life (QOL) is essential in improving long-term outcomes for patients with Major Depressive Disorder (MDD). While previous studies often relied on cross-sectional data, there is a pressing need for stronger evidence based on longitudinal data to better inform the development of effective clinical interventions. By focusing on key depressive symptoms, such interventions have the potential to ultimately enhance QOL in individuals with MDD. Methods: This multi-center prospective study, conducted between 2016 and 2020, enrolled outpatients and inpatients diagnosed with MDD across twelve psychiatric hospitals in China. Longitudinal data on Patient Health Questionnaire - 9 (PHQ-9) and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) was analyzed using an Extended Bayesian Information Criterion (EBIC) graphical least absolute shrinkage and selection operator (gLASSO) network model to explore the connections between depressive symptom changes and QOL changes. Flow network was applied to investigate relationships between individual symptom changes and overall QOL score change, as well as daily functional independence. Results: This study included 818 participants with complete data after 8-week antidepressant treatment. Apart from the overlapping items from PHQ-9 and Q-LES-Q-SF, the three edges between "mood" (delta-QLES2) and "anhedonia" (delta-DEP1), between "physical health" (delta-QLES1) and "sleep problems" (delta-DEP3), and between "physical health" (delta-QLES1) and "sad mood" (delta-DEP2) were the most strong bridges between the cluster of depressive symptoms alleviation and the cluster of QOL change. "Anhedonia" (delta-DEP1), "sad mood" (delta-DEP2) and "loss of energy" (delta-DEP4) had the highest bridge strength between the alleviations of depressive symptoms and the total score change of Q-LES-Q-SF. Anhedonia had the greatest connection with participants' satisfaction with function in daily life. Conclusion: This study highlighted the potential for developing highly effective interventions by targeting on central symptoms, thereby to ultimately improve QOL for patients with MDD.

Gut metagenomes of Asian octogenarians reveal metabolic potential expansion and distinct microbial species associated with aging phenotypes.

While rapid demographic changes in Asia are driving the incidence of chronic aging-related diseases, the limited availability of high-quality in vivo data hampers our ability to understand complex multi-factorial contributions, including gut microbial, to healthy aging. Leveraging a well-phenotyped cohort of community-living octogenarians in Singapore, we used deep shotgun-metagenomic sequencing for high-resolution taxonomic and functional characterization of their gut microbiomes (n = 234). Joint species-level analysis with other Asian cohorts identified distinct age-associated shifts characterized by reduction in microbial richness, and specific Alistipes and Bacteroides species enrichment (e.g., Alistipes shahii and Bacteroides xylanisolvens). Functional analysis confirmed these changes correspond to metabolic potential expansion in aging towards alternate pathways synthesizing and utilizing amino-acid precursors, vis-à-vis dominant microbial guilds producing butyrate in gut from pyruvate (e.g., Faecalibacterium prausnitzii, Roseburia inulinivorans). Extending these observations to key clinical markers helped identify >10 robust microbial associations to inflammation, cardiometabolic and liver health, including potential probiotic species (e.g., Parabacteroides goldsteinii) and pathobionts (e.g., Klebsiella pneumoniae), highlighting the microbiome's role as biomarkers and potential targets for promoting healthy aging.

Safety and activity of lenalidomide in combination with obinutuzumab in patients with relapsed indolent non-Hodgkin lymphoma: a single group, open-label, phase 1/2 trial.

Background: Rituximab and lenalidomide is a preferred option for relapsed indolent B cell non-Hodgkin lymphoma. Obinutuzumab may be a superior combination partner with lenalidomide given enhanced antibody dependent cellular cytotoxicity and phagocytosis compared to rituximab. Our aim was to determine the recommended phase 2 dose, safety, and activity of lenalidomide in combination with fixed dose of obinutuzumab in relapsed and refractory indolent B cell non-Hodgkin lymphoma. Methods: In this single-arm, open-label, phase 1/2 trial, we enrolled patients with relapsed or refractory WHO Grade 1-3A follicular lymphoma, marginal zone lymphoma and small lymphocytic lymphoma and adequate performance status (ECOG 0-2) at the MD Anderson Cancer Center. We excluded patients with evidence of ongoing transformation to aggressive lymphoma. During phase 1, 1000 mg intravenous obinutuzumab was administered with three predefined levels of oral lenalidomide in a 3 + 3 dose escalation design to establish lenalidomide 20 mg as the recommended phase 2 dose. During phase 2, patients received induction therapy with six 28-day cycles of lenalidomide 20 mg with intravenous obinutuzumab 1000 mg. In accordance with our prior experience with lenalidomide plus rituximab, patients who were responding to the combination could receive up to 6 additional cycles (up to 12 cycles in total) of combination therapy. Dosing of obinutuzumab was continued in all responding patients after cycle 6 every 2 months for a total of 30 months from the start of therapy. The decision of number of cycles of combination therapy beyond 6 was at discretion of the investigator and was included to allow individualisation of therapy to maximise response while minimising exposure. The co-primary objectives were to evaluate the safety and overall response, defined as the proportion of patients who achieved a complete or partial response in relapsed and refractory indolent non-Hodgkin lymphoma at the end of induction therapy, according to Cheson and colleagues (2007 criteria). The secondary endpoints were complete response after induction therapy and time to event endpoints including time to progression, progression free survival, and overall survival. Analyses were intent to treat in the efficacy cohort and per-treated in the safety population in all patients who received at least one dose of either investigational agent. This trial is registered with ClinicalTrials.gov, NCT01995669. Findings: Between June 03, 2014, and 07 March 2019, we completed planned enrolment, and 66 patients started therapy including 9 patients in phase 1 and 57 patients in phase 2. All patients were evaluated for safety and the 60 patients treated at the recommended phase 2 dose of lenalidomide 20 mg were evaluable for activity. Grade 3-4 haematological toxicities included neutropenia 21% (14/66) and thrombocytopenia 11% (7/66) with no cases of febrile neutropenia. Grade 3-4 non-haematological toxicities included lung infection 8% (5/66), fatigue 8% (5/66) and rash 6% (4/66). By Cheson 2007 criteria, 90% (54/60, 95% CI: 79-96) achieved an overall response at the end of induction meeting the prespecified activity endpoint. Complete responses were seen in 33% (20/60, 95% CI: 22-47) at the end of induction. Median progression free survival, time to progression and overall survival have not been reached after median follow-up of 41.7 months. Estimated 4-year progression free survival rates were 55% (95% CI: 42-73), time to progression of 56% (95% CI: 43-74) and overall survival of 84% (95% CI: 74-95). Interpretation: Our findings suggest that oral lenalidomide with obinutuzumab is safe and highly active in patients with relapsed and refractory indolent B cell non-Hodgkin lymphoma and is associated with prolonged remission duration. The study is limited by the lack of a control arm leading to cross-trial comparisons to evaluate activity. Future randomised trials comparing this regime to rituximab and lenalidomide are warranted. Funding: Genentech and an MD Anderson Core grant.

Transplantation of miR-145a-5p modified M2 type microglia promotes the tissue repair of spinal cord injury in mice.

BACKGROUND: The traumatic spinal cord injury (SCI) can cause immediate multi-faceted function loss or paralysis. Microglia, as one of tissue resident macrophages, has been reported to play a critical role in regulating inflammation response during SCI processes. And transplantation with M2 microglia into SCI mice promotes recovery of motor function. However, the M2 microglia can be easily re-educated and changed their phenotype due to the stimuli of tissue microenvironment. This study aimed to find a way to maintain the function of M2 microglia, which could exert an anti-inflammatory and pro-repair role, and further promote the repair of spinal cord injury. METHODS: To establish a standard murine spinal cord clip compression model using Dumont tying forceps. Using FACS, to sort microglia from C57BL/6 mice or CX3CR1GFP mice, and further culture them in vitro with different macrophage polarized medium. Also, to isolate primary microglia using density gradient centrifugation with the neonatal mice. To transfect miR-145a-5p into M2 microglia by Lipofectamine2000, and inject miR-145a-5p modified M2 microglia into the lesion sites of spinal cord for cell transplanted therapy. To evaluate the recovery of motor function in SCI mice through behavior analysis, immunofluorescence or histochemistry staining, Western blot and qRT-PCR detection. Application of reporter assay and molecular biology experiments to reveal the mechanism of miR-145a-5p modified M2 microglia therapy on SCI mice. RESULTS: With in vitro experiments, we found that miR-145a-5p was highly expressed in M2 microglia, and miR-145a-5p overexpression could suppress M1 while promote M2 microglia polarization. And then delivery of miR-145a-5p overexpressed M2 microglia into the injured spinal cord area significantly accelerated locomotive recovery as well as prevented glia scar formation and neuron damage in mice, which was even better than M2 microglia transplantation. Further mechanisms showed that overexpressed miR-145a-5p in microglia inhibited the inflammatory response and maintained M2 macrophage phenotype by targeting TLR4/NF-κB signaling. CONCLUSIONS: These findings indicate that transplantation of miR-145a-5p modified M2 microglia has more therapeutic potential for SCI than M2 microglia transplantation from epigenetic perspective.

Technological Advances Are Associated With Better Clinical Outcomes of Percutaneous Coronary Intervention in Patients With Unprotected Left Main Disease.

BACKGROUND: Few large-scale studies have evaluated the effectiveness of percutaneous coronary intervention (PCI) technological advances in the treatment of patients with unprotected left main coronary artery disease (LM-CAD). We aim to identify independent factors that affect the prognosis of PCI in patients with unprotected LM-CAD and to assess the impact of PCI technological advances on long-term clinical outcomes. METHODS AND RESULTS: A total of 4512 consecutive patients who underwent unprotected LM-CAD PCI at Fuwai Hospital from 2004 to 2016 were enrolled. Multivariable Cox proportional hazards model was used to identify which techniques can independently affect the incidence of major adverse cardiac events (MACEs; a composite of cardiac death, myocardial infarction, or target vessel revascularization). The incidence of 3-year MACEs was 9.0% (406/4512). Four new PCI techniques were identified as the independent protective factors of MACEs, including second-generation drug-eluting stents (hazard ratio [HR], 0.61 [95% CI, 0.37-0.99]), postdilatation (HR, 0.75 [95% CI, 0.59-0.94]), final kissing balloon inflation (HR, 0.78 [95% CI, 0.62-0.99]), and using intravascular ultrasound (HR, 0.78 [95% CI, 0.63-0.97]). The relative hazard of 3-year MACEs was reduced by ≈50% with use of all 4 techniques compared with no technique use (HR, 0.53 [95% CI, 0.32-0.87]). CONCLUSIONS: PCI technological advances including postdilatation, second-generation drug-eluting stent, final kissing balloon inflation, and intravascular ultrasound guidance were associated with improved clinical outcomes in patients who underwent unprotected LM-CAD PCI.

Gold Nano Frameworks with Mesopores for Synergistic Immune-Thermal Therapy in Hepatic Carcinoma: A Paradigm Shift in Immune Checkpoint Blockade.

Immune checkpoint blockade (ICB) therapy, while showing promise in various cancers, exhibits limited effectiveness in hepatic carcinoma due to the tumor's immunosuppressive microenvironment (TME) and challenges associated with immune cell infiltration. Efforts to transform the "cold" TME into an "inflamed" state, notably through chemo-immunotherapy, have sparked interest due to their potential to induce immunogenic cell death and augment the infiltration of cytotoxic T lymphocytes (CTLs). Nonetheless, the efficacy of chemo-immunotherapy is often compromised by suboptimal pharmacokinetics, poor tumor accumulation, and off-target toxicity. Herein, in response, we introduce an innovative, milder thermal therapeutic approach leveraging gold nano frameworks with mesopores for the targeted delivery of the immunostimulant imiquimod and NIR-II photothermal therapy. This strategy employs targeted molecule modifications to ensure precise tumor targeting, guided by photoacoustic imaging. Subsequent to mild thermal treatment, there is a release of immunogenic proteins (CRT and HSP90), enhancing tumor immunogenicity. Assisted by imiquimod, substantial CTL infiltration occurs, accompanied by pro-inflammatory factor release (TNF-α, IL-6), transforming M2 macrophages into the M1 phenotype. Ultimately, the proposed strategy combines PD-L1/PD-1 blockade, imiquimod and mild thermal treatment to synergistically enhance tumor immunogenicity, remodel the TME, and restrain hepatic carcinoma, making strides in ICB synergistic immune-thermal therapy.

Combined Effect of Hydrophilic Pore and the Type of Protons on Proton Conductivity in Porous Metal-Organic Frameworks: A Feasible Approach to Achieve a Super Proton Conductor under Hydrated Conditions.

There has been a steady growth of interest in proton-conductive metal-organic frameworks (MOFs) due to their potential utility in proton-exchange membrane fuel cells. To attain a super proton conductivity (>1 × 10-2 S cm-1) in a MOF-based proton conductor is a key step toward practical application. Currently, most studies are focused on enhancing the proton conductivity of porous MOFs by controlling a single factor, such as the type of protons or hydrophilic pore or hydrogen bond. However, a limited contribution from a single factor cannot afford to remarkably increase the proton conductivity of the MOF and form a super proton conductor. Herein, we constructed two distinct porous MOFs, {(H3O+)4[Cu12(ci)12(OH)4(H2O)12]·3H2O·9DMF} (Cu-ci-3D, H2ci = 1H-indazole-5-carboxylic acid, DMF = N,N'-dimethylformamide) and {[Co(Hppca)2]·2HN(CH3)2·CH3OH·2H2O} (Co-ppca-2D, H2ppca = 5-(pyridin-3-yl)-1H-pyrazole-3-carboxylic acid), to tune their proton conductivities at high relative humidity (RH) using the combined effect of hydrophilic pore and the type of protons, ultimately achieving super proton conduction. Excitingly, Cu-ci-3D indeed harvests a super proton conductivity of 1.37 × 10-2 S cm-1 at 353 K and ∼97% RH, superior to some previously reported MOF-based proton conductors. The results present a unique perspective for developing high-performance MOF-based proton conductors and understanding their structure-performance relationships.

Racial and Ethnic Differences in Postoperative Nausea and Vomiting Care.

BACKGROUND: Racial and ethnic differences in health care may result in significant morbidity. The objective of this study was to determine whether there was an association between a patient's race or ethnicity and the receipt of an antiemetic agent preoperatively, during surgery, and in the recovery room. METHODS: A single-institution retrospective study of adult patients (>18 years) who had undergone cancer-related operating room procedures under anesthesia between March 2016 and August 2021 was conducted. A multivariable logistic regression model was fitted to estimate the effects of covariates on antiemetic administration. RESULTS: Of the 60,595 patients included in the study, 3053 (5.0%) self-identified as Asian, 5376 (8.9%) as Black, 8431 (13.9%) as Hispanic or Latino, 42,533 (70.2%) as White, and 1202 (2.0%) as belonging to another racial or ethnic group. Multivariable analyses showed significant associations between a patient's race or ethnicity and the receipt of antiemetics in the preoperative holding area, operating room, and recovery room (all P < .001). In the preoperative holding area, White patients (8962 of 42,533 [21.1%]; odds ratio [OR], 1.188; 95% confidence interval [CI], 1.100-1.283; P < .001) had higher odds of receiving an antiemetic than Black patients (1006 of 5376 [18.7%]). Intraoperatively, the odds were significantly greater for Hispanic or Latino (7323 of 8431 [86.9%]; OR, 1.175; 95% CI, 1.065-1.297; P = .001) and patients who identified as belonging to another race (1078 of 1202 [89.7%]; OR, 1.582; 95% CI, 1.290-1.941; P < .001) than for Black patients (4468 of 5376 [83.1%]). In the recovery room, Asian (499 of 3053 [16.3%]; OR, 1.328; 95% CI: 1.127-1.561; P < .001), Hispanic or Latino (1335 of 8431 [15.8%]; OR, 1.208; 95% CI, 1.060-1.377; P < .005), and White patients (6533 of 42,533 [15.4%]; OR, 1.276; 95% CI, 1.140-1.427; P < .001) had significantly higher odds of receiving antiemetics than Black patients (646 of 5376 [12%]). CONCLUSIONS: This retrospective study suggests significant differences between the administrations of antiemetics to patients of different races or ethnicities, with Black patients often being less likely to receive an antiemetic than patients belonging to all other races or ethnicities.

Cold-hot Janus electrochemical aptamer-based sensor for calibration-free determination of biomolecules.

Real-time, high-frequency measurements of pharmaceuticals, metabolites, exogenous antigens, and other biomolecules in biological samples can provide critical information for health management and clinical diagnosis. Electrochemical aptamer-based (EAB) sensor is a promising analytical technique capable of achieving these goals. However, the issues of insufficient sensitivity, frequent calibration and lack of adapted portable electrochemical device limit its practical application in immediate detection. In response we have fabricated an on-chip-integrated, cold-hot Janus EAB (J-EAB) sensor based on the thermoelectric coolers (TECs). Attributed to the Peltier effect, the enhanced/suppressed current response can be generated simultaneously on cold/hot sides of the J-EAB sensor. The ratio of the current responses on the cold and hot sides was used as the detection signal, enabling rapid on-site, calibration-free determination of small molecules (procaine) as well as macromolecules (SARS-CoV-2 spike protein) in single step, with detection limits of 1 µM and 10 nM, respectively. We have further demonstrated that the J-EAB sensor is effective in improving the ease and usability of the actual detection process, and is expected to provide a universal, low-cost, fast and easy potential analytical tool for other clinically important biomarkers, drugs or pharmaceutical small molecules.

GPR50 regulates neuronal development as a mitophagy receptor.

Neurons rely heavily on high mitochondrial metabolism to provide sufficient energy for proper development. However, it remains unclear how neurons maintain high oxidative phosphorylation (OXPHOS) during development. Mitophagy plays a pivotal role in maintaining mitochondrial quality and quantity. We herein describe that G protein-coupled receptor 50 (GPR50) is a novel mitophagy receptor, which harbors the LC3-interacting region (LIR) and is required in mitophagy under stress conditions. Although it does not localize in mitochondria under normal culturing conditions, GPR50 is recruited to the depolarized mitochondrial membrane upon mitophagy stress, which marks the mitochondrial portion and recruits the assembling autophagosomes, eventually facilitating the mitochondrial fragments to be engulfed by the autophagosomes. Mutations Δ502-505 and T532A attenuate GPR50-mediated mitophagy by disrupting the binding of GPR50 to LC3 and the mitochondrial recruitment of GPR50. Deficiency of GPR50 causes the accumulation of damaged mitochondria and disrupts OXPHOS, resulting in insufficient ATP production and excessive ROS generation, eventually impairing neuronal development. GPR50-deficient mice exhibit impaired social recognition, which is rescued by prenatal treatment with mitoQ, a mitochondrially antioxidant. The present study identifies GPR50 as a novel mitophagy receptor that is required to maintain mitochondrial OXPHOS in developing neurons.

Folic acid capping Bi3+-doped Ag quantum dots for enzyme-like dual-mode recognition of toxic S2- and visual sensing of NO2.

BACKGROUND: NO2- and S2- are two kinds of common toxic anions widely distributed in environmental water, soil and food products. Human beings have suffered a lot of diseases from intake of excessive NO2- or S2-, i.e., infantile methemoglobin, cancer and even to death. Although tremendous efforts have been afforded to monitor NO2- and S2-, most were high instrument-depended with complex processing procedures. To keep food safety and to protect human health, it will be a huge challenge to develop a convenient and efficient way to monitor S2- and NO2- in practice. RESULTS: A kind of folic acid capping Bi3+-doped Ag quantum dots (FA@Bi3+-Ag QDs) was developed for the first time by one-pot homogeneous reduced self-assembly. Not only did FA@Bi3+-Ag QDs possess intrinsic fluorescent property, it expressed synergistic peroxidase-like activity to catalyze the redox of 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2 with Km/vmax of 0.087 mM/6.61 × 10-8 M s-1 and 6.42 mM/6.25 × 10-7 M s-1 respectively. Interestingly, trace S2- could exclusively alter its fluorescent property and peroxidase-like activity, exhibiting significant hypochromic and "turn-on" fluorescent effects. While trace NO2- could make FA@Bi3+-Ag QDs-TMB-H2O2 system hyperchromic. Under the optimized conditions, FA@Bi3+-Ag QDs were applied for dual-mode recognition of S2- and visual sensing of NO2- in real food samples with satisfactory recoveries, i.e., 100.7-107.9 %/95.8-104.7 % and 97.2-104.8 % respectively. The synergistic enzyme-mimic mechanism of FA@Bi3+-Ag QDs and its selective response mechanisms to S2- and NO2- were also proposed. SIGNIFICANCE: This represents the first nanozyme-based FA@Bi3+-Ag QDs system for dual-mode recognition of S2- and visual sensing of NO2-, well meeting the basic requirement in drinking water set by WHO. It will offer a promising way for multi-mode monitoring of different pollution using the same nanozyme-based sensor.

Targeting aging with urolithin A in humans: A systematic review.

Urolithin A (UA) is a gut metabolite derived from ellagic acid. This systematic review assesses the potential geroprotective effect of UA in humans. In five studies including 250 healthy individuals, UA (10-1000 mg/day) for a duration ranging from 28 days to 4 months, showed a dose-dependent anti-inflammatory effect and upregulated some mitochondrial genes, markers of autophagy, and fatty acid oxidation. It did not affect mitochondrial maximal adenosine triphosphate production, biogenesis, dynamics, or gut microbiota composition. UA increased muscle strength and endurance, however, had no effect on anthropometrics, cardiovascular outcomes, and physical function. Unrelated adverse events were mild or moderate. Further research across more physiological systems and longer intervention periods is required.