Exploiting urine-derived induced pluripotent stem cells for advancing precision medicine in cell therapy, disease modeling, and drug testing.

The field of regenerative medicine has witnessed remarkable advancements with the emergence of induced pluripotent stem cells (iPSCs) derived from a variety of sources. Among these, urine-derived induced pluripotent stem cells (u-iPSCs) have garnered substantial attention due to their non-invasive and patient-friendly acquisition method. This review manuscript delves into the potential and application of u-iPSCs in advancing precision medicine, particularly in the realms of drug testing, disease modeling, and cell therapy. U-iPSCs are generated through the reprogramming of somatic cells found in urine samples, offering a unique and renewable source of patient-specific pluripotent cells. Their utility in drug testing has revolutionized the pharmaceutical industry by providing personalized platforms for drug screening, toxicity assessment, and efficacy evaluation. The availability of u-iPSCs with diverse genetic backgrounds facilitates the development of tailored therapeutic approaches, minimizing adverse effects and optimizing treatment outcomes. Furthermore, u-iPSCs have demonstrated remarkable efficacy in disease modeling, allowing researchers to recapitulate patient-specific pathologies in vitro. This not only enhances our understanding of disease mechanisms but also serves as a valuable tool for drug discovery and development. In addition, u-iPSC-based disease models offer a platform for studying rare and genetically complex diseases, often underserved by traditional research methods. The versatility of u-iPSCs extends to cell therapy applications, where they hold immense promise for regenerative medicine. Their potential to differentiate into various cell types, including neurons, cardiomyocytes, and hepatocytes, enables the development of patient-specific cell replacement therapies. This personalized approach can revolutionize the treatment of degenerative diseases, organ failure, and tissue damage by minimizing immune rejection and optimizing therapeutic outcomes. However, several challenges and considerations, such as standardization of reprogramming protocols, genomic stability, and scalability, must be addressed to fully exploit u-iPSCs' potential in precision medicine. In conclusion, this review underscores the transformative impact of u-iPSCs on advancing precision medicine and highlights the future prospects and challenges in harnessing this innovative technology for improved healthcare outcomes.

Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Randomized Clinical Trial of 10 and 14 Days.

BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).

Association of RASGRP1 polymorphism with vascular complications in Chinese diabetic patients with glycemic control and antihypertensive treatment.

BACKGROUND: Studies have shown that RASGRP1 was potently associated with the onset of type 2 diabetes mellitus (T2DM), and RASGRP1 rs7403531 was significantly correlated with islet function in T2DM patients. However, the effect of RASGRP1 polymorphism on blood glucose and blood pressure in T2DM patients after continuous treatment has yet to be fully elucidated. OBJECTIVE: This study aimed to explore the association between RASGRP1 genetic polymorphism and cardiovascular complications in T2DM patients, so as to provide more evidence for the individualized treatment of T2DM patients. METHODS: We retrospectively analyzed a large-scale multicenter drug clinical study cohort that based on a 2 × 2 factorial (glucose control axis and blood pressure lowering axis) randomized controlled design, with follow-up for 5 years. The major vascular endpoint events included cardiovascular death, non-fatal stroke, coronary heart disease, new-onset or worsening renal disease, and diabetic retinopathy. RASGRP1 rs12593201, rs56254815 and rs7403531 were finally selected as candidate single nucleotide polymorphisms. Mixed linear model and Cox hazard ratio (HR) model were used for data analysis with IBM SPSS (version 20.0 for windows; Chicago, IL). RESULTS: Our study enrolled 1357 patients with high-risk diabetes, with a mean follow-up duration of 4.8 years. RASGRP1 rs7403531 was associated with vascular events in hypoglycemic and antihypertensive therapy. Specifically, compared with CC carriers, patients with CT/TT genotype had fewer major microvascular events (HR = 0.41, 95% confidence interval (CI) 0.21-0.80, P = 0.009), and reduced the risk of major eye disease events (HR = 0.44, 95% CI 0.20-0.94, P = 0.03). For glucose lowering axis, CT/TT carriers had a lower risk of secondary nephropathy (HR = 0.48, 95% CI 0.25-0.92, P = 0.03) in patients with standard glycemic control. For blood pressure lowering axis, all cerebrovascular events (HR = 2.24, 95% CI 1.11-4.51, P = 0.025) and stroke events (HR = 2.07, 95% CI 1.03-4.15, P = 0.04) were increased in patients with CC genotype compared to those with CT/TT genotype in the placebo group, respectively. Furthermore, patients with CC genotype showed a reduced risk of major cerebrovascular events in antihypertensive group (HR = 0.36, 95% CI 0.15-0.86, P = 0.021). For RASGRP1 rs56254815, compared with the AA genotype carriers, the systolic blood pressure of AG/GG carriers in the antihypertensive group decreased by 1.5mmhg on average (P = 0.04). In the placebo group, the blood pressure of AG/GG carriers was 1.7mmHg higher than that of AA carriers (P = 0.02). CONCLUSION: We found that patients with G allele of RASGRP1 (rs56254815) showed a better antihypertensive therapy efficacy in T2DM patients. The rs7403531 T allele could reduce the risk of major microvascular events and major eye diseases in T2DM patients receiving either hypoglycemic or antihypertensive therapy. Our findings suggest that RASGRP1 genetic polymorphism might predict the cardiovascular complications in T2DM patients.

Psychometric validation of the PERMA-profiler for well-being in Chinese adults.

Well-being is one of the central topics in psychology, and research on this topic has shifted from emotional experiences to flourishing life in recent years. Seligman's PERMA model is a prominent theory in this shift. However, this model is proposed in Western culture and has yet to be empirically validated in the Chinese context. The present research aims to examine the applicability of the five-dimension PERMA-Profiler in Chinese culture, which has been developed based on the PERMA model. A sample of 1468 Chinese adults participated in the research. After translation and validation, a series of psychometric analyses were conducted to examine the internal consistency reliability, construct validity, convergent and discriminant validity, and factorial invariance across genders. The PERMA-Profiler Chinese showed high Cronbach's alpha coefficients (α = 0.79-0.88), good divergent (r = -0.19 to -0.38) and convergent validity (r = 0.53-0.85), as well as satisfactory structural validity. Results of the structural validity demonstrated a better fit to the first-order model with five correlated factors after modification (χ2/df = 4.65, RMSEA = 0.058, SRMR = 0.030, CFI = 0.943, TLI = 0.924) than the second-order model with a higher-order factor of well-being. However, the engagement dimension of the PERMA-Profiler Chinese could be improved further. In conclusion, the PERMA model is applicable to the Chinese culture, and the PERMA-Profiler provides a valid measure of well-being for Chinese adults.

Effects of positive psychological interventions on positive and negative emotions in depressed individuals: a systematic review and meta-analysis.

BACKGROUND: Positive psychological interventions (PPIs) are known to be effective in alleviating depression. However, the effect of PPIs on positive and negative emotions in depressed participants is not unclear. AIMS: To systematically investigate the effects of PPIs on positive and negative emotions in depressed individuals. METHODS: 6 databases were searched for randomized controlled trials of PPIs in individuals with depressive disorders or depressive symptoms. Hedges' g value was computed using a random-effects model to determine effect sizes. RESULTS: 14 trials from 13 studies were included. Our meta-analysis showed that PPIs had significant but small effects on improving positive affect (g = 0.33, p = .02), life satisfaction (g = 0.26, p = .03), happiness (g = 0.62, p = .03) and depression (g = -0.32, p = .001), and negligible effects on improving well-being (g = 0.13, p = .24) and negative affect (g = -0.15, p = .31). Subgroup analyses of depression showed that PPIs have experienced benefits in improving depression in most subgroups. In addition, none of the subgroup analyses performed for outcomes other than depression found PPIs to be more effective than controls. CONCLUSION: PPIs can improve positive affect, life satisfaction, happiness and depression in depressed individuals, but further studies are needed to validate their effects on well-being, and negative affect.

Vulnerable brain regions in adolescent major depressive disorder: A resting-state functional magnetic resonance imaging activation likelihood estimation meta-analysis.

BACKGROUND: Adolescent major depressive disorder (MDD) is a significant mental health concern that often leads to recurrent depression in adulthood. Resting-state functional magnetic resonance imaging (rs-fMRI) offers unique insights into the neural mechanisms underlying this condition. However, despite previous research, the specific vulnerable brain regions affected in adolescent MDD patients have not been fully elucidated. AIM: To identify consistent vulnerable brain regions in adolescent MDD patients using rs-fMRI and activation likelihood estimation (ALE) meta-analysis. METHODS: We performed a comprehensive literature search through July 12, 2023, for studies investigating brain functional changes in adolescent MDD patients. We utilized regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) analyses. We compared the regions of aberrant spontaneous neural activity in adolescents with MDD vs healthy controls (HCs) using ALE. RESULTS: Ten studies (369 adolescent MDD patients and 313 HCs) were included. Combining the ReHo and ALFF/fALFF data, the results revealed that the activity in the right cuneus and left precuneus was lower in the adolescent MDD patients than in the HCs (voxel size: 648 mm3, P < 0.05), and no brain region exhibited increased activity. Based on the ALFF data, we found decreased activity in the right cuneus and left precuneus in adolescent MDD patients (voxel size: 736 mm3, P < 0.05), with no regions exhibiting increased activity. CONCLUSION: Through ALE meta-analysis, we consistently identified the right cuneus and left precuneus as vulnerable brain regions in adolescent MDD patients, increasing our understanding of the neuropathology of affected adolescents.

Phytoplankton-derived polysaccharides and microbial peptidoglycans are key nutrients for deep-sea microbes in the Mariana Trench.

BACKGROUND: The deep sea represents the largest marine ecosystem, driving global-scale biogeochemical cycles. Microorganisms are the most abundant biological entities and play a vital role in the cycling of organic matter in such ecosystems. The primary food source for abyssal biota is the sedimentation of particulate organic polymers. However, our knowledge of the specific biopolymers available to deep-sea microbes remains largely incomplete. One crucial rate-limiting step in organic matter cycling is the depolymerization of particulate organic polymers facilitated by extracellular enzymes (EEs). Therefore, the investigation of active EEs and the microbes responsible for their production is a top priority to better understand the key nutrient sources for deep-sea microbes. RESULTS: In this study, we conducted analyses of extracellular enzymatic activities (EEAs), metagenomics, and metatranscriptomics from seawater samples of 50-9305 m from the Mariana Trench. While a diverse array of microbial groups was identified throughout the water column, only a few exhibited high levels of transcriptional activities. Notably, microbial populations actively transcribing EE genes involved in biopolymer processing in the abyssopelagic (4700 m) and hadopelagic zones (9305 m) were primarily associated with the class Actinobacteria. These microbes actively transcribed genes coding for enzymes such as cutinase, laccase, and xyloglucanase which are capable of degrading phytoplankton polysaccharides as well as GH23 peptidoglycan lyases and M23 peptidases which have the capacity to break down peptidoglycan. Consequently, corresponding enzyme activities including glycosidases, esterase, and peptidases can be detected in the deep ocean. Furthermore, cell-specific EEAs increased at 9305 m compared to 4700 m, indicating extracellular enzymes play a more significant role in nutrient cycling in the deeper regions of the Mariana Trench. CONCLUSIONS: Transcriptomic analyses have shed light on the predominant microbial population actively participating in organic matter cycling in the deep-sea environment of the Mariana Trench. The categories of active EEs suggest that the complex phytoplankton polysaccharides (e.g., cutin, lignin, and hemicellulose) and microbial peptidoglycans serve as the primary nutrient sources available to deep-sea microbes. The high cell-specific EEA observed in the hadal zone underscores the robust polymer-degrading capacities of hadal microbes even in the face of the challenging conditions they encounter in this extreme environment. These findings provide valuable new insights into the sources of nutrition, the key microbes, and the EEs crucial for biopolymer degradation in the deep seawater of the Mariana Trench. Video Abstract.

Effects of pH-shifting and ultrasound on the structural and emulsifying properties of peanut globulin fractions.

This work investigated and compared the structural and emulsifying properties of peanut globulin fractions (conarachin and arachin) after ultrasonication (US) and pH2.5-shifting treatments, singly and in combination. Results showed that pH2.5-shifting was more effective in degrading peanut protein subunits and unfolding their structures than US treatment. Conarachin tended to aggregate during US and pH2.5-shifting treatments possibly due to higher free sulfhydryl content, while high molecular weight arachin tended to disaggregate during these treatments. pH2.5-shifting or US+pH2.5-shifting treatments significantly increased the surface hydrophobicity of conarachin (from 72 to 314) and arachin (from 336 to 888), which may be responsible for the enhancement of protein emulsifying activity. All treatments significantly improved the physical stability of arachin-stabilized emulsions with higher absolute potentials but lowered that of conarachin-stabilized emulsions. However, pH2.5-shifting or US+pH2.5-shifting treatments could improve the stability of conarachin-stabilized emulsions in the presence of salts.

Remodeling of the Intra-Conduit Inflammatory Microenvironment to Improve Peripheral Nerve Regeneration with a Neuromechanical Matching Protein-Based Conduit.

Peripheral nerve injury (PNI) remains a challenging area in regenerative medicine. Nerve guide conduit (NGC) transplantation is a common treatment for PNI, but the prognosis of NGC treatment is unsatisfactory due to 1) neuromechanical unmatching and 2) the intra-conduit inflammatory microenvironment (IME) resulting from Schwann cell pyroptosis and inflammatory-polarized macrophages. A neuromechanically matched NGC composed of regenerated silk fibroin (RSF) loaded with poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (P:P) and dimethyl fumarate (DMF) are designed, which exhibits a matched elastic modulus (25.1 ± 3.5 MPa) for the peripheral nerve and the highest 80% elongation at break, better than most protein-based conduits. Moreover, the NGC can gradually regulate the intra-conduit IME by releasing DMF and monitoring sciatic nerve movements via piezoresistive sensing. The combination of NGC and electrical stimulation modulates the IME to support PNI regeneration by synergistically inhibiting Schwann cell pyroptosis and reducing inflammatory factor release, shifting macrophage polarization from the inflammatory M1 phenotype to the tissue regenerative M2 phenotype and resulting in functional recovery of neurons. In a rat sciatic nerve crush model, NGC promoted remyelination and functional and structural regeneration. Generally, the DMF/RSF/P:P conduit provides a new potential therapeutic approach to promote nerve repair in future clinical treatments.

Effect of Comfort Care on Perioperative Outcomes and Postoperative Recovery of Breast Cancer Patients.

Objective: The objective of this study was to evaluate the effects of comfort care on perioperative outcomes and postoperative recovery of breast cancer patients. Evaluating comfort care is important in the context of breast cancer surgery because it can potentially alleviate pain, improve patient comfort, enhance postoperative recovery, and reduce complications, ultimately leading to better patient outcomes. Methods: Between March 2020 and December 2021, 78 patients undergoing breast cancer surgery at our hospital were randomly assigned to receive either routine nursing (routine group) or comfort care (experimental group). The comfort care intervention included various components such as health education, preoperative care, intraoperative care, postoperative care, pain care, and psychological care. The routine group received standard nursing care following medical advice. Results: The patient characteristics between the two groups were comparable. Comfort care resulted in significantly higher visual analog scale (VAS) scores, indicating reduced pain, and better improvement in functional recovery of the upper limb compared to routine nursing. Comfort care was also associated with better postoperative recovery, as evidenced by lower self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores. The experimental group had a significantly lower incidence of complications compared to the routine group. Additionally, the experimental group reported better 24-hour comfort and higher nursing satisfaction. Conclusion: In conclusion, comfort care effectively reduces postoperative pain, promotes postoperative recovery, improves patient emotions, lowers the incidence of complications, and enhances comfort and care satisfaction in breast cancer patients undergoing radical surgery. These findings highlight the importance of incorporating comfort care interventions in the perioperative management of breast cancer patients. Further research and implementation of comfort care strategies may have implications for improving clinical practice and patient outcomes in the future.

[Retracted] microRNA­146b promotes neuroblastoma cell growth through targeting NUMB.

[This retracts the article DOI: 10.3892/etm.2020.8623.].

Do Scholars Respond Faster Than Google Trends in Discussing COVID-19 Issues? An Approach to Textual Big Data.

Background: The COVID-19 pandemic has posed various difficulties for policymakers, such as the identification of health issues, establishment of policy priorities, formulation of regulations, and promotion of economic competitiveness. Evidence-based practices and data-driven decision-making have been recognized as valuable tools for improving the policymaking process. Nevertheless, due to the abundance of data, there is a need to develop sophisticated analytical techniques and tools to efficiently extract and analyze the data. Methods: Using Oxford COVID-19 Government Response Tracker, we categorize the policy responses into 6 different categories: (a) containment and closure, (b) health systems, (c) vaccines, (d) economic, (e) country, and (f) others. We proposed a novel research framework to compare the response times of the scholars and the general public. To achieve this, we analyzed more than 400,000 research abstracts published over the past 2.5 years, along with text information from Google Trends as a proxy for topics of public concern. We introduced an innovative text-mining method: coherent topic clustering to analyze the huge number of abstracts. Results: Our results show that the research abstracts not only discussed almost all of the COVID-19 issues earlier than Google Trends did, but they also provided more in-depth coverage. This should help policymakers identify core COVID-19 issues and act earlier. Besides, our clustering method can better reflect the main messages of the abstracts than a recent advanced deep learning-based topic modeling tool. Conclusion: Scholars generally have a faster response in discussing COVID-19 issues than Google Trends.

Case Report: Enhancing lead extraction techniques: a novel approach using a loop formed by an ablation catheter and a gooseneck snare.

The difficulty and complexity of lead extraction procedures increase with the age of the lead to be extracted. The extraction of old (>20 years) leads is more time-consuming and requires advanced tools and a complex technique. In this case, we retrieved a very old (>30 years) lead using a loop formed by a catheter and a gooseneck snare. The catheter was rotated to remove the lead-bound sites. The lead was successfully retrieved using a Needle's Eye Snare.

Evaluation of the lncRNA-miRNA-mRNA ceRNA network in lungs of miR-147 -/- mice.

Background: Previous studies have documented important roles for microRNA-147 (miR-147) in inflammation, radiation-induced injury, cancer, and a range of other diseases. Murine lungs exhibit high levels of miRNA, mRNA, and lncRNA expression. However, very little research to date has focused on the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks associated with miR-147, and the regulation of lncRNAs and miRNAs in this setting remains poorly understood. Methods: After establishing a miR-147-/- model mouse, samples of lung tissue were harvested for RNA-sequencing, and differentially expressed lncRNAs, miRNAs, and mRNAs were identified. The miRNA targets of these lncRNAs and the identified miRNAs were first overlapped to facilitate the prediction of target mRNAs, with analyses then examining the overlap between these targets and mRNAs that were differentially expressed. Then, these target mRNAs were subjected to pathway enrichment analyses. These results were ultimately used to establish a miR-147-related ceRNA network. Results: Relative to wild-type mice, the lungs of miR-147-/- mice exhibited 91, 43, and 71 significantly upregulated lncRNAs, miRNAs, and mRNAs, respectively, together with 114, 31, and 156 that were significantly downregulated. The lncRNA-miRNA-mRNA network established based on these results led to the identification of Kcnh6 as a differentially expressed hub gene candidate and enabled the identification of a range of regulatory relationships. KEGG pathway enrichment showed that the mRNA targets of differentially expressed lncRNAs and miRNAs in the mice were associated with tumor-related signaling, endometrial cancer, bladder cancer, and ErbB signaling. Conclusion: These results suggest that the identified ceRNA network in miR-147-/- mice shapes tumor-associated signaling activity, with miR-147 potentially regulating various lncRNAs and miRNAs through Kcnh6, ultimately influencing tumorigenesis. Future studies of the lncRNA, miRNA, and mRNA regulatory targets shown to be associated with miR-147 in the present study may ultimately lead to the identification of novel clinically relevant targets through which miR-147 shapes the pathogenesis of cancer and other diseases.

Evaluation of the hepatotoxicity of Psoralea corylifolia L. based on a zebrafish model.

Objective: Psoralea corylifolia L. (FP) has received increasing attention due to its potential hepatotoxicity. Methods: In this study, zebrafish were treated with different concentrations of an aqueous extract of FP (AEFP; 40, 50, or 60 µg/mL), and the hepatotoxic effects of tonicity were determined by the mortality rate, liver morphology, fluorescence area and intensity of the liver, biochemical indices, and pathological tissue staining. The mRNA expression of target genes in the bile acid metabolic signaling pathway and lipid metabolic pathway was detected by qPCR, and the mechanism of toxicity was initially investigated. AEFP (50 µg/mL) was administered in combination with FXR or a peroxisome proliferator-activated receptor α (PPARα) agonist/inhibitor to further define the target of toxicity. Results: Experiments on toxic effects showed that, compared with no treatment, AEFP administration resulted in liver atrophy, a smaller fluorescence area in the liver, and a lower fluorescence intensity (p < 0.05); alanine transaminase (ALT), aspartate transaminase (AST), and γ-GT levels were significantly elevated in zebrafish (p < 0.01), and TBA, TBIL, total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were elevated to different degrees (p < 0.05); and increased lipid droplets in the liver appeared as fatty deposits. Molecular biological validation revealed that AEFP inhibited the expression of the FXR gene, causing an increase in the expression of the downstream genes SHP, CYP7A1, CYP8B1, BSEP, MRP2, NTCP, peroxisome proliferator-activated receptor γ (PPARγ), ME-1, SCD-1, lipoprotein lipase (LPL), CPT-1, and CPT-2 and a decrease in the expression of PPARα (p < 0.05). Conclusion: This study demonstrated that tonic acid extracts are hepatotoxic to zebrafish through the inhibition of FXR and PPARα expression, thereby causing bile acid and lipid metabolism disorders.

Alterations of sleep deprivation on brain function: A coordinate-based resting-state functional magnetic resonance imaging meta-analysis.

BACKGROUND: Sleep deprivation is a prevalent issue that impacts cognitive function. Although numerous neuroimaging studies have explored the neural correlates of sleep loss, inconsistencies persist in the reported results, necessitating an investigation into the consistent brain functional changes resulting from sleep loss. AIM: To establish the consistency of brain functional alterations associated with sleep deprivation through systematic searches of neuroimaging databases. Two meta-analytic methods, signed differential mapping (SDM) and activation likelihood estimation (ALE), were employed to analyze functional magnetic resonance imaging (fMRI) data. METHODS: A systematic search performed according to PRISMA guidelines was conducted across multiple databases through July 29, 2023. Studies that met specific inclu-sion criteria, focused on healthy subjects with acute sleep deprivation and reported whole-brain functional data in English were considered. A total of 21 studies were selected for SDM and ALE meta-analyses. RESULTS: Twenty-one studies, including 23 experiments and 498 subjects, were included. Compared to pre-sleep deprivation, post-sleep deprivation brain function was associated with increased gray matter in the right corpus callosum and decreased activity in the left medial frontal gyrus and left inferior parietal lobule. SDM revealed increased brain functional activity in the left striatum and right central posterior gyrus and decreased activity in the right cerebellar gyrus, left middle frontal gyrus, corpus callosum, and right cuneus. CONCLUSION: This meta-analysis consistently identified brain regions affected by sleep deprivation, notably the left medial frontal gyrus and corpus callosum, shedding light on the neuropathology of sleep deprivation and offering insights into its neurological impact.

Nutritional status and nutritional intervention of older inpatients in China.

BACKGROUND: Malnutrition is a critical issue among older inpatients, yet limited large-scale research related to this issue has been conducted in China. This study aimed to examine the nutritional status and support of older inpatients in China, assess the associations between disease categories and malnutrition on admission, and explore effective nutritional intervention. METHODS: A total of 24,139 older participants from the China Nutrition Fundamental Data 2020 Project were included. Malnutrition was measured by the Global Leadership Initiative on Malnutrition criteria. Adjusted odds ratios (aORs) were calculated using logistic analysis. RESULTS: The overall frequency of malnutrition on admission was 18.9%. Participants with infections were more likely to have malnutrition (aOR = 1.929, 95% CI 1.486-2.504). Risks that were also noted for malnutrition included neoplasms (aOR = 1.822, 95% CI 1.697-1.957), hemic and lymphatic diseases (aOR = 1.671, 95% CI 1.361-2.051), nervous system diseases (aOR = 1.222, 95% CI 1.126-1.326), respiratory diseases (aOR = 1.613, 95% CI 1.490-1.746), and digestive system diseases (aOR = 1.462, 95% CI 1.357-1.577). Further, 32.26% inpatients with malnutrition during hospitalization didn't receive nutritional support. Oral nutrition supplements, enteral tube feeding, and parenteral nutrition were associated with stable or improved nutritional status. CONCLUSIONS: Older inpatients were at a high risk for malnutrition but did not receive adequate nutritional intervention. More resources and attention need to be devoted to the nutritional status of older inpatients and targeted nutritional support.

NLRP3 knockout in mice provided protection against Serratia marcescens-induced acute pneumonia by decreasing PD-L1 and PD-1 expression in macrophages.

Antibiotic-resistant Serratia marcescens (Sm) is known to cause bloodstream infections, pneumonia, etc. The nod-like receptor family, pyrin domain-containing 3 (NLRP3), has been implicated in various lung infections. Yet, its role in Sm-induced pneumonia was not well understood. In our study, we discovered that deletion of Nlrp3 in mice significantly improved Sm-induced survival rates, reduced bacterial loads in the lungs, bronchoalveolar lavage fluid (BALF), and bloodstream, and mitigated the severity of acute lung injury (ALI) compared to wild-type (WT) mice. Mechanistically, we observed that 24 h post-Sm infection, NLRP3 inflammasome activation occurred, leading to gasdermin D NH2-terminal (GSDMD-NT)-induced pyroptosis in macrophages and IL-1ß secretion. The NLRP3 or NLRP3 inflammasome influenced the expression PD-L1 and PD-1, as well as the count of PD-L1 or PD-1-expressing macrophages, alveolar macrophages, interstitial macrophages, PD-L1-expressing neutrophils, and the count of macrophage receptors with collagenous structure (MARCO)-expressing macrophages, particularly MARCO+ alveolar macrophages. The frequency of MARCO+ alveolar macrophages, PD-1 expression, particularly PD-1+ interstitial macrophages were negatively or positively correlated with the Sm load, respectively. Additionally, IL-1ß levels in BALF correlated with three features of acute lung injury: histologic score, protein concentration and neutrophil count in BALF. Consequently, our findings suggest that Nlrp3 deletion offers protection agaisnt acute Sm pneumonia in mice by inhibiting inflammasome activation and reducing Sm infection-induced PD-L1/PD-1 or MARCO expression, particularly in macrophages. This highlights potential therapeutic targets for Sm and other gram-negative bacteria-induced acute pneumonia.