miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells.

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

Activatable Fluorescence and Bio/Chemiluminescence Probes for Aminopeptidases: From Design to Biomedical Applications.

Aminopeptidases are exopeptidases that catalyze the cleavage of amino acid residues from the N-terminal fragment of protein or peptide substrates. Owing to their function, they play important roles in protein maturation, signal transduction, cell-cycle control, and various disease mechanisms, notably in cancer pathology. To gain better insights into their function, molecular imaging assisted by fluorescence and bio/chemiluminescence probes has become an indispensable method to their superiorities, including excellent sensitivity, selectivity, and real-time and noninvasive imaging. Numerous efforts are made to develop activatable probes that can effectively enhance efficiency and accuracy as well as minimize the side effects. This review is classified according to the type of aminopeptidases, summarizing some recent works on the design, work mechanism, and sensing, imaging, and theranostic performance of their activatable probe. Finally, the current challenges are outlined in developing activatable probes for aminopeptidases and provide possible solutions for future advancements.

High sensitivity troponins and mortality in the population with metabolic dysfunction-associated steatotic liver disease.

Given the global high prevalence of MASLD and its poor CVD prognosis, it is essential to perform risk stratification for MASLD patients. The specific impact of High Sensitivity Troponins (hs-cTn ) on mortality in MASLD patients remains unexplored.  The NHANES databases from 1999 to 2004, which include data on high-sensitivity cardiac troponin (hs-cTn) levels and comorbidities, were linked with the most recent mortality dataset. Myocardial injury was determined using the 99th upper reference limits (URL) for hs-cTn.  Our study included 3460 MASLD patients. The mean follow-up duration was 192 months, during which 1074 (23%) MASLD participants died from all-cause mortality, and 363 (7.3%) died from CVD mortality. Our findings indicate that MASLD patients with elevated levels of hs-cTnT (> 99th URL) exhibit increased risks of all-cause mortality [adjusted hazard ratio (aHR) = 1.93] and CVD mortality (aHR = 2.4). Similar results were observed for hs-cTnI, where the aHRs for all-cause mortality and CVD mortality were 2.03 and 2.97, respectively. Furthermore, we identified a nonlinear dose-response relationship between hs-cTn levels and the risk of mortality (P for nonlinearity < 0.001).  Our findings suggest that hs-cTn can predict mortality risk in MASLD, aiding clinicians in risk-stratifying this population. Therefore, we recommend considering hs-cTn detection in individuals with MASLD to effectively assess their future mortality risk.

Sequential and domain-specific processing mechanisms for dual cognitive-emotional conflict.

This study aimed to investigate how the cognitive control system resolves conflicts when cognitive and emotional conflicts occur simultaneously, and how it performs. To achieve this, a factorial task-crossing design was employed, combining the spatial Simon task and the face-word emotional interference task, allowing cognitive and emotional conflicts to occur concurrently within a single trial. The results revealed that the Simon cognitive conflict was only associated with N2 and early SP, while it did not affect the amplitude of N450 and late SP. Conversely, the face-word emotional conflict affected the amplitude of N450 and late SP, but had no impact on N2 and early SP. These findings demonstrate the adaptive sequencing organization and domain specificity in cognitive-emotional dual conflict processing, which reflects the precise and flexible orchestration and strategic adjustments of the cognitive control system. The results contribute to a better understanding of the dynamic and temporal processes involved in the cognitive control of multiple conflicts.

PI3Kγ inhibition circumvents inflammation and vascular leak in SARS-CoV-2 and other infections.

Virulent infectious agents such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and methicillin-resistant Staphylococcus aureus (MRSA) induce tissue damage that recruits neutrophils, monocyte, and macrophages, leading to T cell exhaustion, fibrosis, vascular leak, epithelial cell depletion, and fatal organ damage. Neutrophils, monocytes, and macrophages recruited to pathogen-infected lungs, including SARS-CoV-2-infected lungs, express phosphatidylinositol 3-kinase gamma (PI3Kγ), a signaling protein that coordinates both granulocyte and monocyte trafficking to diseased tissues and immune-suppressive, profibrotic transcription in myeloid cells. PI3Kγ deletion and inhibition with the clinical PI3Kγ inhibitor eganelisib promoted survival in models of infectious diseases, including SARS-CoV-2 and MRSA, by suppressing inflammation, vascular leak, organ damage, and cytokine storm. These results demonstrate essential roles for PI3Kγ in inflammatory lung disease and support the potential use of PI3Kγ inhibitors to suppress inflammation in severe infectious diseases.

Spatiotemporally Controllable Covalent Bonding of RNA for Multi-Protein Interference.

Many diseases are associated with genetic mutation and expression of mutated proteins, such as cancers. Therapeutic approaches that selectively target the synthesis process of multiple proteins show greater potential compared to single-protein approaches in oncological diseases. However, conventional agents to regulate the synthesis of multiple protein still suffer from poor spatiotemporal selectivity and stability. Here, a new method using a dye-peptide conjugate, PRFK, for multi-protein interference with spatiotemporal selectivity and reliable stability, is reported. By using the peptide sequence that targets tumor cells, PRFK can be efficiently taken up, followed by specific binding to the KDELR (KDEL receptor) protein located in the endoplasmic reticulum (ER). The dye generates 1O2 under light irradiation, enabling photodynamic therapy. This process converts the furan group into a cytidine-reactive intermediate, which covalently binds to mRNA, thereby blocking protein synthesis. Upon treating 4T1 cells, the proteomics data show alterations in apoptosis, ferroptosis, proliferation, migration, invasion, and immune infiltration, suggesting that multi-protein interference leads to the disruption of cellular physiological activities, ultimately achieving tumor treatment. This study presents a multi-protein interference probe with the potential for protein interference within various subcellular organelles in the future.

The association between lactate dehydrogenase to serum albumin ratio and in-hospital mortality in patients with pulmonary embolism: a retrospective analysis of the MIMIC-IV database.

Background: Lactate dehydrogenase (LDH) and albumin (ALB) were found to be significantly correlated with mortality in pulmonary embolism (PE) patients. However, data regarding the LDH/ALB ratio (LAR) in patients with acute PE are scanty. Therefore, the aim of this study was to investigate the association between LAR and the risk of mortality in patients with acute PE. Methods: A retrospective cohort study was conducted on patients with acute PE represented in the Medical Information Mart for Intensive Care IV (MIMIC-IV). A receiver operating characteristic (ROC) curve analysis and calibration curve were used to assess the accuracy of the LAR for predicting mortality in patients with acute PE. We utilized Cox regression analysis to determine adjusted hazard ratios (HR) and 95% confidence interval (CI). Survival curves were used to evaluate a connection between the LAR and prognosis in patients with acute PE. Results: The study comprised 581 patients, and the 30-day all-cause mortality rate was 7.7%. We observed a higher LAR in the non-survival group compared to the surviving group (21.24 ± 21.22 vs. 8.99 ± 7.86, p < 0.0001). The Kaplan-Meier analysis showed that patients with an elevated LAR had a significantly lower likelihood of surviving the 30-day mortality compared to those with a low LAR. Cox regression analysis showed that LAR (HR = 1.04, 95% CI: 1.03-1.05) might have associations with 30-day mortality in patients with acute PE. This result was supported by sensitivity analyses. According to the results of the ROC curve analysis, the LAR's prediction of 30-day mortality in patients with acute PE yielded an area under the ROC curve of 0.73. A calibration curve showed LAR is well calibrated. Conclusion: Our research suggests LAR monitoring may be promising as a prognostic marker among patients with acute PE.

Immunocytes interact directly with cancer cells in the tumor microenvironment: one coin with two sides and future perspectives.

The tumor microenvironment is closely linked to the initiation, promotion, and progression of solid tumors. Among its constitutions, immunologic cells emerge as critical players, facilitating immune evasion and tumor progression. Apart from their indirect impact on anti-tumor immunity, immunocytes directly influence neoplastic cells, either bolstering or impeding tumor advancement. However, current therapeutic modalities aimed at alleviating immunosuppression from regulatory cells on effector immune cell populations may not consistently yield satisfactory results in various solid tumors, such as breast carcinoma, colorectal cancer, etc. Therefore, this review outlines and summarizes the direct, dualistic effects of immunocytes such as T cells, innate lymphoid cells, B cells, eosinophils, and tumor-associated macrophages on tumor cells within the tumor microenvironment. The review also delves into the underlying mechanisms involved and presents the outcomes of clinical trials based on these direct effects, aiming to propose innovative and efficacious therapeutic strategies for addressing solid tumors.

[Air Pollutant Spatiotemporal Evolution Characteristics and Effects on Human Health in Xi'an City].

Xi'an is the political, economic, and cultural center of northwest China with a developed industry. Air pollution incidents have brought great challenges to the high-quality development of the social economy. It is vital to study air pollution characteristics and clarify their impact on human health. In this study, we first analyzed the spatiotemporal variations in air pollutants in the study region from 2015 to 2021. Then, the air quality index (AQI), aggregate air quality index (AAQI), and health risk-based air quality index (HAQI) were used to assess health risks. Based on these, the AirQ2.2.3 model was used to quantify health effects. The results showed that the major pollutants were PM10, PM2.5, and O3. The main pollution characteristics of the study area were terrain characteristics and the mixed pollution of anthropogenic emissions. Compared to that of AQI, AAQI and HAQI showed better classification performance for pollution levels. HAQI revealed that approximately 80 % of the population was exposed to unhealthy air throughout the year in the study region. People were most exposed to unhealthy air in winter, followed by autumn and spring, and the least in summer. The AirQ2.2.3 model quantified the total mortality proportions attributable to PM2.5, PM10, SO2, CO, NO2, and O3, which were 0.99 %, 2.04 %, 0.41 %, 1.72 %, 8.76 %, and 3.67 %, respectively. The attributable proportion of mortality of the respiratory system and cardiovascular diseases was consistent with the change rule of total mortality.

Favorable outcome of neoadjuvant endocrine treatment than surgery-first in female HR-positive/HER2-negative breast cancer patients-A NCDB analysis (2010-2016).

PURPOSE: To assess the efficacy of neoadjuvant endocrine therapy in female HR-positive/HER2-negative breast cancer patients. DATA AND METHODS: We identified female patients aged ≥18 years with cT1-4N0-XM0, HR(+), and HER2(-) breast cancer from the National Cancer Database. The patients who underwent surgery first were categorized as "surgery-first," while those who received NET before surgery were classified as "NET." Propensity score-matching, Cox proportional-hazard model, variance inflation factors, and interaction analysis were employed to estimate the correlation between NET and survival outcomes. RESULTS: Among 432,387 cases, 2914 NET patients and 2914 surgery-first patients were matched. Compared with the surgery-first group, the NET group received less adjuvant chemotherapy (p < 0.001). Furthermore, the NET group exhibited higher survival probabilities compared with the surgery-first group (3 years: 91.4% vs. 82.1%; 5 years: 82.1% vs. 66.8%). Multivariate Cox analysis indicated that NET was associated with improved OS (surgery-first vs. NET: HR 2.17, 95% CI: 1.93-2.44). Age over 55 years old, having public insurance, higher CDCC score, higher NSBR grade, ER(+)PR(-), and advanced clinical stage were related to worse OS (all p < 0.05). There was an interaction between age, race, income, and home and treatment regimen (all p < 0.05). CONCLUSION: NET may be a more effective treatment procedure than surgery-first in female HR-positive/HER2-negative, non-metastatic breast cancer patients. Future clinical studies with more detailed data will provide higher-level evidence-based data.

Repeatability and Agreement of 4 Biometers Measuring Corneal Astigmatism in Eyes With Irregular Corneal Astigmatism Component.

PURPOSE: To investigate the repeatability and agreement of corneal astigmatism measurements in eyes with irregular corneal astigmatism component (ICAC) using four devices: IOLMaster 700 biometer, Lenstar 900 biometer, iTrace, and Pentacam. DESIGN: Prospective cross-sectional reliability analysis. METHODS: Sixty-four eyes (52 patients) with ICAC were examined three times using the four devices. The eye with ICAC in this study is defined as the cornea has a certain degree of irregular astigmatism (asymmetric and/or skewed bowtie pattern of corneal topography according to corneal topography classification), accompanied with total corneal higher-order aberrations in the 4 mm zone of 0.3 µm or greater. Corneal astigmatism was evaluated using three categories: anterior corneal astigmatism (ACA), posterior corneal astigmatism, and total corneal astigmatism (TCA). The repeatability was determined using the ∆Ast (arithmetic mean of vector differences among three repeated corneal astigmatism measurements). Bland-Altman plots and astigmatism vector analyses were employed to assess agreement. RESULTS: The IOLMaster 700 (∆Ast = 0.27 ± 0.20 D) showcased higher repeatability in ACA measurements compared to iTrace (∆Ast = 0.37 ± 0.38 D, P = .040) and Pentacam (∆Ast = 0.50 ± 0.22 D, P < .001), and paralleled the performance of Lenstar 900 (∆Ast = 0.31 ± 0.26 D, P = .338). The Pentacam (∆Ast = 0.09 ± 0.07 D, P < .001) demonstrated superior repeatability in posterior corneal astigmatism, whereas the IOLMaster 700 (∆Ast = 0.33 ± 0.23 D, P < .001) excelled in TCA. The IOLMaster 700 exhibited good agreement with either Lenstar 900 or iTrace, characterized by narrow 95% limits of agreement and clinically acceptable vector differences. Conversely, vector differences between Pentacam and the other three devices in ACA and TCA measurements were clinically significant, exceeding 0.50 D (all P < .05). CONCLUSIONS: In terms of repeatability of corneal astigmatism measurements in eyes with ICAC, the IOLMaster 700 and Lenstar 900 outperformed iTrace and Pentacam. While the IOLMaster 700 can be used interchangeably with either Lenstar 900 or iTrace, the Pentacam is not interchangeable with the other three devices.

Effects of high-flow nasal cannula oxygen therapy in bronchiectasis and hypercapnia: a retrospective observational study.

BACKGROUND: The effectiveness of high-flow nasal cannula (HFNC) therapy in patients with bronchiectasis experiencing hypercapnia remains unclear. Our aim was to retrospectively analyze the short-term outcomes of HFNC therapy in such patients, and to further explore the predictors of HFNC treatment failure in this particular patient population. METHODS: A retrospective review was conducted on patients with bronchiectasis who received HFNC (n = 70) for hypercapnia (arterial partial pressure of carbon dioxide, PaCO2 ≥ 45 mmHg) between September 2019 and September 2023. RESULTS: In the study population, 30% of patients presented with acidemia (arterial pH < 7.35) at baseline. Within 24 h of HFNC treatment, there was a significant reduction in PaCO2 levels by a mean of 4.0 ± 12.7 mmHg (95% CI -7.0 to -1.0 mmHg). Concurrently, arterial pH showed a statistically significant increase with a mean change of 0.03 ± 0.06 (95% CI 0.01 to 0.04). The overall hospital mortality rate in our study was 17.5%. The median length of hospital stay was 11.0 days (interquartile range [IQR] 8.0 to 16.0 days). Sub-analysis revealed no statistically significant differences in hospital mortality (19.0% vs. 20.4%, p = 0.896), length of hospital stay (median 14.0 days [IQR 9.0 to 18.0 days] vs. 10.0 days [IQR 7.0 to 16.0 days], p = 0.117) and duration of HFNC application (median 5.0 days [IQR 2.0 to 8.5 days] vs. 6.0 days [IQR 4.9 to 9.5 days], p = 0.076) between the acidemia group and the non-acidemia group (arterial pH ≥ 7.35). However, more patients in the non-acidemia group had do-not-intubate orders. The overall treatment failure rate for HFNC was 28.6%. Logistic regression analysis identified the APACHE II score (OR 1.24 per point) as the independent predictor of HFNC failure. CONCLUSIONS: In patients with bronchiectasis and hypercapnia, HFNC as an initial respiratory support can effectively reduce PaCO2 level within 24 h of treatment. A high APACHE II score has emerged as a prognostic indicator for HFNC treatment failure. These observations highlight randomized controlled trials to meticulously evaluate the efficacy of HFNC in this specific population.

Mesencephalic astrocyte-derived neurotrophic factor inhibits cervical cancer progression via regulating macrophage phenotype.

BACKGROUND: Cervical cancer is a common gynecologic malignant tumor, but the critical factors affecting cervical cancer progression are still not well demonstrated. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been widely recognized as an anti-inflammatory factor to regulate macrophage polarization. In this study, the effect and mechanism of MANF on cervical cancer were preliminarily explored. METHODS AND RESULTS: Kaplan-Meier curve was used to show the overall survival time of the involved cervical cancer patients with high and low MANF expression in cervical cancer tissues. MANF was highly expressed in peritumoral tissues of cervical carcinoma by using immunohistochemistry and western blot. MANF mRNA level was detected by using qRT-PCR. Dual-labeled immunofluorescence showed MANF was mainly expressed in macrophages of cervical peritumoral tissues. Moreover, MANF-silenced macrophages promoted HeLa and SiHa cells survival, migration, invasion and EMT via NF-κB signaling activation. The results of tumor formation in nude mice indicated MANF-silenced macrophages promoted cervical tumor formation in vivo. CONCLUSION: Our study reveals an inhibitory role of MANF in cervical cancer progression, indicating MANF as a new and valuable therapeutic target for cervical cancer treatment.

Research on Dynamic Response under the External Impact of Paper Honeycomb Sandwich Board.

The dynamic mechanical behavior and cushioning performance of honeycomb sandwich panels, which are extensively employed in product cushioning packaging due to their exceptional energy absorption capabilities, were examined using a combination of experimental and numerical methods. Several factors, such as maximum acceleration-static stress, cushioning coefficient-static stress, and other curves, were analyzed under various impact conditions. The simulated stress-strain, deformation modes, cushioning coefficients, and other parameters demonstrate consistency with the experimental results. The acceleration, maximum compression, and cushioning coefficient obtained from the experiment and simulation calculation were 30.68 g, 15.44 mm, and 2.65, and 31.96 g, 14.91 mm, and 2.79, respectively. The results indicate that all error values were less than 5%, confirming the precision and reliability of the model. Furthermore, the model was utilized to simulate and predict the cushioning performance of honeycomb sandwich panels with different cell structures and paper thicknesses. These results provide a solid basis for enhancing the design of subsequent honeycomb element structures.

Myocardial reperfusion injury exacerbation due to ALDH2 deficiency is mediated by neutrophil extracellular traps and prevented by leukotriene C4 inhibition.

BACKGROUND AND AIMS: The Glu504Lys polymorphism in the aldehyde dehydrogenase 2 (ALDH2) gene is closely associated with myocardial ischaemia/reperfusion injury (I/RI). The effects of ALDH2 on neutrophil extracellular trap (NET) formation (i.e. NETosis) during I/RI remain unknown. This study aimed to investigate the role of ALDH2 in NETosis in the pathogenesis of myocardial I/RI. METHODS: The mouse model of myocardial I/RI was constructed on wild-type, ALDH2 knockout, peptidylarginine deiminase 4 (Pad4) knockout, and ALDH2/PAD4 double knockout mice. Overall, 308 ST-elevation myocardial infarction patients after primary percutaneous coronary intervention were enrolled in the study. RESULTS: Enhanced NETosis was observed in human neutrophils carrying the ALDH2 genetic mutation and ischaemic myocardium of ALDH2 knockout mice compared with controls. PAD4 knockout or treatment with NETosis-targeting drugs (GSK484, DNase1) substantially attenuated the extent of myocardial damage, particularly in ALDH2 knockout. Mechanistically, ALDH2 deficiency increased damage-associated molecular pattern release and susceptibility to NET-induced damage during myocardial I/RI. ALDH2 deficiency induced NOX2-dependent NETosis via upregulating the endoplasmic reticulum stress/microsomal glutathione S-transferase 2/leukotriene C4 (LTC4) pathway. The Food and Drug Administration-approved LTC4 receptor antagonist pranlukast ameliorated I/RI by inhibiting NETosis in both wild-type and ALDH2 knockout mice. Serum myeloperoxidase-DNA complex and LTC4 levels exhibited the predictive effect on adverse left ventricular remodelling at 6 months after primary percutaneous coronary intervention in ST-elevation myocardial infarction patients. CONCLUSIONS: ALDH2 deficiency exacerbates myocardial I/RI by promoting NETosis via the endoplasmic reticulum stress/microsomal glutathione S-transferase 2/LTC4/NOX2 pathway. This study hints at the role of NETosis in the pathogenesis of myocardial I/RI, and pranlukast might be a potential therapeutic option for attenuating I/RI, particularly in individuals with the ALDH2 mutation.

Low-grade mucoepidermoid carcinoma mimicking benign cystic lesions in the salivary gland: A diagnostic dilemma.

Mucoepidermoid carcinoma (MEC) is a common malignancy arising in the parotid gland. The diagnosis of MEC is typically based on its morphological features alone, characteristically containing mucocytes, intermediate cells and epidermoid cells. However, when cystic degeneration is diffuse, it is challenging to distinguish MEC from other benign cystic tumors. This is a case report of a 58-year-old Caucasian man who presented with a parotid mass. H&E sections of the mass reveal multiloculated cysts lined by bland-looking epithelium with only rare papillary architectures. The papillary proliferation contains mucocytes, and epidermoid cells highlighted by the p63 immunohistochemistry study. The diagnosis was confirmed by FISH result of positive MAML2 (11q21) rearrangement. Patient underwent parotidectomy and is disease-free 6 months post-surgery. MEC with cystic degeneration is a common diagnostic pitfall which can mimic many benign lesions in the salivary gland. We present a rare case with MEC with extensive cystic change, its molecular and pathologic findings and review the diagnostic features of MEC, its benign mimickers and useful tools for distinguishing these entities.

Higher ultra processed foods intake is associated with low muscle mass in young to middle-aged adults: a cross-sectional NHANES study.

Design: Ultra-processed foods (UPFs) have become a pressing global health concern, prompting investigations into their potential association with low muscle mass in adults. Methods: This cross-sectional study analyzed data from 10,255 adults aged 20-59 years who participated in the National Health and Nutritional Examination Survey (NHANES) during cycles spanning from 2011 to 2018. The primary outcome, low muscle mass, was assessed using the Foundation for the National Institutes of Health (FNIH) definition, employing restricted cubic splines and weighted multivariate regression for analysis. Sensitivity analysis incorporated three other prevalent definitions to explore optimal cut points for muscle quality in the context of sarcopenia. Results: The weighted prevalence of low muscle mass was 7.65%. Comparing the percentage of UPFs calories intake between individuals with normal and low muscle mass, the values were found to be similar (55.70 vs. 54.62%). Significantly linear associations were observed between UPFs consumption and low muscle mass (P for non-linear = 0.7915, P for total = 0.0117). Upon full adjustment for potential confounding factors, participants with the highest UPFs intake exhibited a 60% increased risk of low muscle mass (OR = 1.60, 95% CI: 1.13 to 2.26, P for trend = 0.003) and a decrease in ALM/BMI (ß = -0.0176, 95% CI: -0.0274 to -0.0077, P for trend = 0.003). Sensitivity analysis confirmed the consistency of these associations, except for the International Working Group on Sarcopenia (IWGS) definition, where the observed association between the highest quartiles of UPFs (%Kcal) and low muscle mass did not attain statistical significance (OR = 1.35, 95% CI: 0.97 to 1.87, P for trend = 0.082). Conclusion: Our study underscores a significant linear association between higher UPFs consumption and an elevated risk of low muscle mass in adults. These findings emphasize the potential adverse impact of UPFs on muscle health and emphasize the need to address UPFs consumption as a modifiable risk factor in the context of sarcopenia.

A Universal and Programmable Platform based on Fluorescent Peptide-Conjugated Probes for Detection of Proteins in Organelles of Living Cells.

Realizing protein analysis in organelles of living cells is of great significance for developing diagnostic and therapeutic methods of diseases. Fluorescent-labeled antibodies with well imaging performance and high affinity are classical biochemical tools for protein analysis, while due to the inability to effectively enter into cells, not to mention organelles and the uncontrollable reaction sites that might cause antibodies inactivation when chemically modification, they are hard to apply to living cells. Inspired by the structure of fluorescent-labeled antibodies, we designed as a universal detection platform that was based on the peptide-conjugated probes (PCPs) and consisted of three parts: a) a rotor type fluorescent molecular scaffold for conjugation and signal output; b) the cell penetration protein recognition unit; c) the subcellular organelle targeting unit. In living cells, PCPs could firstly localize at organelles and then proceed protein specific recognition, thus jointly leading to the restriction of twisted intramolecular charge transfer and activation of fluorescence signal. As a proof-of-concept, six different proteins in three typical intracellular organelles could be detected by our platform through simply replacing the recognition sequence of proteins and matching organelle targeting units. The position and intensity of fluorescence signals demonstrated specificity of PCPs and universality of the platform.