Deep eutectic solvent (TMAH·5H2O/Urea) with low viscosity for cellulose dissolution at room temperature.

A deep eutectic solvent (DES) formulated with tetramethylammonium hydroxide pentahydrate /urea (TMAH·5H2O/Urea) was designed for the first time to dissolve cellulose at room temperature. The optimized system, characterized by a 1:3 M ratio, demonstrates the capability to dissolve approximately 7.5 wt% cellulose, boasting a high degree of polymerization (DP = 526). Notably, both the pure DES and 4.0 wt% cellulose/TMAH·5H2O/Urea mixtures manifests low viscosity, establishing its potential as an effective spinning aid in fiber manufacturing. The structural analyses shows that the cellulose crystal type shifts from type I to type II form, accompanied by a reduction in both crystallinity and DP. A pivotal aspect of this research involves determining Kamlet-Taft parameters for TMAH·5H2O/Urea-DES with different molar ratios. The results reveal these solvate DESs exhibit the high hydrogen bond basicity, which enables them to easily form hydrogen bonds with hydroxyl groups of cellulose and demonstrate good cellulose solubility. In conclusion, this solvent system presents notable advantages, including straightforward synthesis procedures, low viscosity, and well cellulose solubility, paving the way for new approaches and techniques in cellulose utilization.

Quantitative susceptibility mapping of multiple system atrophy and Parkinson's disease correlates with neurotransmitter reference maps.

BACKGROUND: Multiple system atrophy (MSA) and Parkinson's disease (PD) are neurodegenerative disorders characterized by α-synuclein pathology, disrupted iron homeostasis and impaired neurochemical transmission. Considering the critical role of iron in neurotransmitter synthesis and transport, our study aims to identify distinct patterns of whole-brain iron accumulation in MSA and PD, and to elucidate the corresponding neurochemical substrates. METHODS: A total of 122 PD patients, 58 MSA patients and 78 age-, sex-matched health controls underwent multi-echo gradient echo sequences and neurological evaluations. We conducted voxel-wise and regional analyses using quantitative susceptibility mapping to explore MSA or PD-specific alterations in cortical and subcortical iron concentrations. Spatial correlation approaches were employed to examine the topographical alignment of cortical iron accumulation patterns with normative atlases of neurotransmitter receptor and transporter densities. Furthermore, we assessed the associations between the colocalization strength of neurochemical systems and disease severity. RESULTS: MSA patients exhibited increased susceptibility in the striatal, midbrain, cerebellar nuclei, as well as the frontal, temporal, occipital lobes, and anterior cingulate gyrus. In contrast, PD patients displayed elevated iron levels in the left inferior occipital gyrus, precentral gyrus, and substantia nigra. The excessive iron accumulation in MSA or PD correlated with the spatial distribution of cholinergic, noradrenaline, glutamate, serotonin, cannabinoids, and opioid neurotransmitters, and the degree of this alignment was related to motor deficits. CONCLUSIONS: Our findings provide evidence of the interaction between iron accumulation and non-dopamine neurotransmitters in the pathogenesis of MSA and PD, which inspire research on potential targets for pharmacotherapy.

Quantitative radiomics analysis of imaging features in adults and children Mycoplasma pneumonia.

Purpose: This study aims to explore the value of clinical features, CT imaging signs, and radiomics features in differentiating between adults and children with Mycoplasma pneumonia and seeking quantitative radiomic representations of CT imaging signs. Materials and methods: In a retrospective analysis of 981 cases of mycoplasmal pneumonia patients from November 2021 to December 2023, 590 internal data (adults:450, children: 140) randomly divided into a training set and a validation set with an 8:2 ratio and 391 external test data (adults:121; children:270) were included. Using univariate analysis, CT imaging signs and clinical features with significant differences (p < 0.05) were selected. After segmenting the lesion area on the CT image as the region of interest, 1,904 radiomic features were extracted. Then, Pearson correlation analysis (PCC) and the least absolute shrinkage and selection operator (LASSO) were used to select the radiomic features. Based on the selected features, multivariable logistic regression analysis was used to establish the clinical model, CT image model, radiomic model, and combined model. The predictive performance of each model was evaluated using ROC curves, AUC, sensitivity, specificity, accuracy, and precision. The AUC between each model was compared using the Delong test. Importantly, the radiomics features and quantitative and qualitative CT image features were analyzed using Pearson correlation analysis and analysis of variance, respectively. Results: For the individual model, the radiomics model, which was built using 45 selected features, achieved the highest AUCs in the training set, validation set, and external test set, which were 0.995 (0.992, 0.998), 0.952 (0.921, 0.978), and 0.969 (0.953, 0.982), respectively. In all models, the combined model achieved the highest AUCs, which were 0.996 (0.993, 0.998), 0.972 (0.942, 0.995), and 0.986 (0.976, 0.993) in the training set, validation set, and test set, respectively. In addition, we selected 11 radiomics features and CT image features with a correlation coefficient r greater than 0.35. Conclusion: The combined model has good diagnostic performance for differentiating between adults and children with mycoplasmal pneumonia, and different CT imaging signs are quantitatively represented by radiomics.

Interventions to Prevent Falls in Community-Dwelling Older Adults: US Preventive Services Task Force Recommendation Statement.

Importance: Falls are the leading cause of injury-related morbidity and mortality among older adults in the US. In 2018, 27.5% of community-dwelling adults 65 years or older reported at least 1 fall in the past year and 10.2% reported a fall-related injury. In 2021, an estimated 38 742 deaths resulted from fall-related injuries. Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the effectiveness and harms of primary care-relevant interventions to prevent falls and fall-related morbidity and mortality in community-dwelling adults 65 years or older. Population: Community-dwelling adults 65 years or older at increased risk of falls. Evidence Assessment: The USPSTF concludes with moderate certainty that exercise interventions provide a moderate net benefit in preventing falls and fall-related morbidity in older adults at increased risk for falls. The USPSTF concludes with moderate certainty that multifactorial interventions provide a small net benefit in preventing falls and fall-related morbidity in older adults at increased risk for falls. Recommendation: The USPSTF recommends exercise interventions to prevent falls in community-dwelling adults 65 years or older who are at increased risk for falls. (B recommendation) The USPSTF recommends that clinicians individualize the decision to offer multifactorial interventions to prevent falls to community-dwelling adults 65 years or older who are at increased risk for falls. Existing evidence indicates that the overall net benefit of routinely offering multifactorial interventions to prevent falls is small. When determining whether this service is appropriate for an individual, patients and clinicians should consider the balance of benefits and harms based on the circumstances of prior falls, presence of comorbid medical conditions, and the patient's values and preferences. (C recommendation).

Mesenchymal stem cells and their derived exosomes for the treatment of COVID-19.

Coronavirus disease 2019 (COVID-19) is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection typically presents with fever and respiratory symptoms, which can progress to severe respiratory distress syndrome and multiple organ failure. In severe cases, these complications may even lead to death. One of the causes of COVID-19 deaths is the cytokine storm caused by an overactive immune response. Therefore, suppressing the overactive immune response may be an effective strategy for treating COVID-19. Mesenchymal stem cells (MSCs) and their derived exosomes (MSCs-Exo) have potent homing abilities, immunomodulatory functions, regenerative repair, and antifibrotic effects, promising an effective tool in treating COVID-19. In this paper, we review the main mechanisms and potential roles of MSCs and MSCs-Exo in treating COVID-19. We also summarize relevant recent clinical trials, including the source of cells, the dosage and the efficacy, and the clinical value and problems in this field, providing more theoretical references for the clinical use of MSCs and MSCs-Exo in the treatment of COVID-19.

Needs-based considerations for the role of low-dose aspirin along the CV risk continuum.

Cardiovascular disease (CVD) remains the leading cause of death worldwide. The risk of a cardiovascular (CV) event is not static and increases along a continuum, making identification and management complex. Aspirin has been the cornerstone of antiplatelet therapy in CV risk reduction and remains the only antiplatelet agent with current guideline recommendations throughout the CV risk continuum. In light of recent trials, the role of aspirin in CVD prevention in asymptomatic patients has been downgraded in clinical guidelines. However, a substantial proportion of asymptomatic patients have underlying conditions, such as advanced subclinical atherosclerosis that are associated with high CV risk. Advanced subclinical atherosclerosis has not been extensively investigated in patients in clinical trials but in the absence of significant bleeding risks, patients with subclinical atherosclerosis may particularly benefit from preventive aspirin therapy. Recent studies and clinical guidelines support the need for a personalized treatment approach for these patients, balancing their risk of future CV events against their relative bleeding risk. In this commentary, we first discussed various tools and strategies currently available for assessing CV and bleeding risks; we then provided two hypothetical cases to outline how these tools can be implemented for optimal management of patients with no prior CV events who, nonetheless, are susceptible to CVD. The first case details a young and apparently healthy patient with underlying advanced subclinical atherosclerosis; whereas the second case describes a patient with recently diagnosed type 2 diabetes mellitus who is at higher risk of CVD than their non-diabetic counterparts. For both cases, we considered patient clinical characteristics, CV and bleeding risks, as well as other risk factors to evaluate the appropriate treatment strategy and determine whether patients would obtain a net clinical benefit from low-dose aspirin therapy. These cases can serve as examples to guide clinical decision-making on the use of low-dose aspirin for primary CVD prevention and improve CVD management via a personalized approach.

TLR8 agonist selgantolimod regulates Kupffer cell differentiation status and impairs HBV entry into hepatocytes via an IL-6-dependent mechanism.

OBJECTIVE: Achieving HBV cure will require novel combination therapies of direct-acting antivirals and immunomodulatory agents. In this context, the toll-like receptor 8 (TLR8) agonist selgantolimod (SLGN) has been investigated in preclinical models and clinical trials for chronic hepatitis B (CHB). However, little is known regarding its action on immune effectors within the liver. Our aim was to characterise the transcriptomic changes and intercellular communication events induced by SLGN in the hepatic microenvironment. DESIGN: We identified TLR8-expressing cell types in the human liver using publicly available single-cell RNA-seq data and established a method to isolate Kupffer cells (KCs). We characterised transcriptomic and cytokine KC profiles in response to SLGN. SLGN's indirect effect was evaluated by RNA-seq in hepatocytes treated with SLGN-conditioned media (CM) and quantification of HBV parameters following infection. Pathways mediating SLGN's effect were validated using transcriptomic data from HBV-infected patients. RESULTS: Hepatic TLR8 expression takes place in the myeloid compartment. SLGN treatment of KCs upregulated monocyte markers (eg, S100A12) and downregulated genes associated with the KC identity (eg, SPIC). Treatment of hepatocytes with SLGN-CM downregulated NTCP and impaired HBV entry. Cotreatment with an interleukin 6-neutralising antibody reverted the HBV entry inhibition. CONCLUSION: Our transcriptomic characterisation of SLGN sheds light into the programmes regulating KC activation. Furthermore, in addition to its previously described effect on established HBV infection and adaptive immunity, we show that SLGN impairs HBV entry. Altogether, SLGN may contribute through KCs to remodelling the intrahepatic immune microenvironment and may thus represent an important component of future combinations to cure HBV infection.

Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Oral AL01211 in Healthy Chinese Volunteers.

BACKGROUND AND OBJECTIVE: Aberrant accumulation of glycosphingolipids (GSLs) in the lysosome leads to GSL storage diseases. Glucosylceramide synthase inhibitors (GCSi) have the potential to treat several GSL storage diseases by reducing the synthesis of the disease-causing GSLs. AL01211 is a potent oral GCSi under investigation for Type 1 Gaucher disease and Fabry disease. Here, we evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of AL01211 in healthy Chinese volunteers. METHODS: AL01211 was tested in a Phase 1, single-center, randomized, double-blind, placebo-controlled study with single-dose (15 and 60 mg) and multiple-dose (30 mg) arms. RESULTS: Results of AL01211 demonstrated dose-dependent pharmacokinetics, rapid absorption (median time to maximum plasma concentration [tmax] 2.5-4 hours), relatively slow clearance rate (mean apparent total clearance from plasma [CL/F] 88.3-200 L/h) and the mean terminal half-life above 30 hours. Repeated once-daily oral administration of AL01211 for 14 days had an approximately 2-fold accumulation, reaching steady-state levels between 7 and 10 days, and led to a 73% reduction in plasma glucosylceramide (GL1) on Day 14. AL01211 was safe and well tolerated, with no identified serious adverse events. CONCLUSION: AL01211 showed a favorable pharmacokinetic, pharmacodynamics, safety, and tolerability profile in healthy Chinese volunteers. These data support the further clinical development of AL01211 as a therapy for GSL storage diseases. CLINICAL TRIAL REGISTRY: Clinical Trial Registry no. CTR20221202 ( http://www.chinadrugtrials.org.cn ) registered on 6 June 2022 and ChiCTR2200061431 ( http://www.chictr.org.cn ) registered on 24 June 2022.

Umbilical Cord Blood and UC-MSCs Combined with Low-Dose Immunosuppressant in the Treatment of Elderly Patients with Pure Red Cell Aplastic: A Case Series.

INTRODUCTION: At present, cyclosporine (CsA) is the first-line treatment for Pure Red Cell Aplasia (PRCA), but CsA administration can be associated with a number of side effects due to its high toxicity. Therefore, it is urgent to explore a safe and effective treatment for elderly patients who cannot be treated with conventional doses of CsA, especially those with multiple complications. Allogeneic Stem Cell Transplantation (ASCT) for PRCA is a promising treatment, but reports of using umbilical cord blood (UCB) are very rare. CASE PRESENTATION: In this report, UCB and umbilical cord mesenchymal stem cells (UC-MSCs) combined with low-dose CsA (1-3mg/kg/d) were used to treat 3 elderly patients who were diagnosed with PRCA combined with multiple complications in heart, lung, and renal. The treatments were successful without complications, and 12 months after stem cell infusion, the blood tests of the patients came normal. Moreover, the function of the liver, heart, and kidney continued to be stable. CONCLUSION: This report provides an effective regimen of using UCB and UC-MSCs combined with low-dose CsA (1-3 mg/kg/d) to treat PRCA, especially for elderly patients with multiple complications who cannot use the conventional dosage.

Epidemiological characteristics and antibody kinetics of elderly population with booster vaccination following both Omicron BA.5 and XBB waves in China.

After the termination of zero-COVID-19 policy, the populace in China has experienced both Omicron BA.5 and XBB waves. Considering the poor antibody responses and severe outcomes observed among the elderly following infection, we conducted a longitudinal investigation to examine the epidemiological characteristics and antibody kinetics among 107 boosted elderly participants following the Omicron BA.5 and XBB waves. We observed that 96 participants (89.7%) were infected with Omicron BA.5, while 59 (55.1%) participants were infected with Omicron XBB. Notably, 52 participants (48.6%) experienced dual infections of both Omicron BA.5 and XBB. The proportion of symptomatic cases appeared to decrease following the XBB wave (18.6%) compared to that after the BA.5 wave (59.3%). Omicron BA.5 breakthrough infection induced lower neutralizing antibody titers against XBB.1.5, BA.2.86, and JN.1, while reinfection with Omicron XBB broadened the antibody responses against all measured Omicron subvariants and may alleviate the wild type-vaccination induced immune imprinting. Boosted vaccination type and comorbidities were the significant factors associated with antibody responses. Updated vaccines based on emerging severe acute respiratory syndrome coronavirus 2 variants are needed to control the Coronavirus Disease 2019 pandemic in the elderly.

Predictors of MOUD referral among persons with involvement in the criminal legal system.

INTRODUCTION: Opioid use disorder (OUD) is a significant cause of opioid-related fatality, and while medications to treat OUD (MOUD) are effective, disparities remain in the access and uptake of such medications. This study investigated factors that may influence referral to and initiation of MOUD treatment. METHODS: Data from electronic medical records of 677 patients with a history of criminal legal system involvement in a recovery program were used to examine the flow of MOUD referral. RESULTS: Among patients identified as potentially eligible for MOUD treatment, about 38.0 percent were referred and 18.8 percent were confirmed to initiate MOUD treatment. Logistic regression analyses highlighted female gender and unemployment due to incarceration as positive and negative predictors of referral, respectively. The Chi-square test revealed that women and uninsured patients were more likely to initiate referred MOUD treatment. CONCLUSIONS: Data highlight the need for greater connection between referral agencies and MOUD treatment providers, considering factors that may influence referral.

Fluorinated Surface Engineering towards High-rate and Durable Potassium-ion Battery.

Solid electrolyte interphase (SEI) crucially affects the rate performance and cycling lifespan, yet to date more extensive research is still needed in potassium-ion batteries. We report an ultra-thin and KF-enriched SEI triggered by tuned fluorinated surface design in electrode. Our results reveal that fluorination engineering alters the interfacial chemical environment to facilitate inherited electronic conductivity, enhance adsorption ability of potassium, induce localized surface polarization to guide electrolyte decomposition behavior for SEI formation, and especially, enrich the KF crystals in SEI by self-sacrifice from C-F bond cleavage. Hence, the regulated fluorinated electrode with generated ultra-thin, uniform, and KF-enriched SEI shows improved capacity of 439.3 mAh g-1 (3.82 mAh cm--2), boosted rate performance (202.3 mAh g-1 at 8.70 mA cm-2) and durable cycling performance (even under high loading of ~8.7 mg cm-2). We expect this practical engineering principle to open up new opportunities for upgrading the development of potassium-ion batteries.

Strictosamide promotes wound healing through activation of the PI3K/AKT pathway.

Nauclea officinalis, as a Chinese medicine in Hainan province, had the effect of treating lower limb ulcers, burn infections. In this paper, we studied the effect of Strictosamide (STR), the main bioactive compound in Nauclea officinals, on wound healing and explored its internal mechanism. Firstly, the wound healing potential of STR was evaluated in a rat model, demonstrating its ability to expedite wound healing, mitigate inflammatory infiltration, and enhance collagen deposition. Additionally, immunofluorescence analysis revealed that STR up-regulated the expression of CD31 and PCNA. Subsequently, target prediction, protein-protein interaction (PPI), gene ontology (GO), and pathway enrichment analyses were used to obtain potential targets, specific biological processes, and molecular mechanisms of STR for the potential treatment of wound healing. Furthermore, molecular docking was conducted to predict the binding affinity between STR and its associated targets. Additionally, in vivo and in vitro experiments confirmed that STR could increase the expression of P-PI3K, P-AKT and P-mTOR by activating the PI3K/AKT signaling pathway. In summary, this study provided a new explanation for the mechanism by which STR promotes wound healing through network pharmacology, suggesting that STR may be a new candidate for treating wound.

An algorithm to identify patients aged 0-3 with rare genetic disorders.

BACKGROUND: With over 7000 Mendelian disorders, identifying children with a specific rare genetic disorder diagnosis through structured electronic medical record data is challenging given incompleteness of records, inaccurate medical diagnosis coding, as well as heterogeneity in clinical symptoms and procedures for specific disorders. We sought to develop a digital phenotyping algorithm (PheIndex) using electronic medical records to identify children aged 0-3 diagnosed with genetic disorders or who present with illness with an increased risk for genetic disorders. RESULTS: Through expert opinion, we established 13 criteria for the algorithm and derived a score and a classification. The performance of each criterion and the classification were validated by chart review. PheIndex identified 1,088 children out of 93,154 live births who may be at an increased risk for genetic disorders. Chart review demonstrated that the algorithm achieved 90% sensitivity, 97% specificity, and 94% accuracy. CONCLUSIONS: The PheIndex algorithm can help identify when a rare genetic disorder may be present, alerting providers to consider ordering a diagnostic genetic test and/or referring a patient to a medical geneticist.

CT-guided ozone-mediated lumbar-renal sympathetic denervation for resistant hypertension treatment: A pilot single-arm clinical trial.

BACKGROUND: Renal sympathetic denervation (RDN) reduces blood pressure (BP). METHODS: This single-arm open-label study enrolled patients with resistant hypertension (RH) and treat them by CT-guided ozone mediated lumbar-renal sympathetic denervation (L-RDN). The primary endpoint was to assess the changes of BP over 24-h ambulatory BP monitoring (ABPM) and to evaluate the anti-hypertensive medication burden (AHMB) at 3-month follow-up. This study was registered in Chictr.org.cn (ChiCTR2300071375). RESULTS: 17 patients (mean age 65.12 ± 10.77 years) with AHMB of 4.12 ± 1.11 were enrolled. After the procedure, 7 patients (46.7 %) matched the criteria for antihypertensive medication reduction. The AHMB decreased to 3.87 ± 0.96 for the whole objectives and from 3.87 ± 0.96 to 3.55 ± 0.78 for patients with normal baseline renal function. On top of the lessened AHMB, L-RDN further reduced morning systolic BP (SBP) by -8.6 ± 4.0 mmHg (p = 0.034) and diastolic BP (DBP) by -4.6 ± 2.1 mmHg (p = 0.032) for all participants and morning SBP by -13.2 ± 3.6 mmHg (p < 0.001), morning DBP by -6.2 ± 2.4 mmHg (p = 0.011) and daytime SBP by -4.1 ± 1.6 mmHg (p = 0.009) for those with normal baseline renal function at 3-month of follow-up. No adverse events were reported intra- and post operation. CONCLUSIONS: CT-guided ozone-mediated L-RDN might be an innovative approach of RDN for treating RH. Confirmatory studies are warranted.

Efficacy and safety of PD-1/PD-L1 inhibitors in elderly patients with advanced non-small cell lung cancer.

OBJECTIVE: This study aimed to investigate the efficacy and safety of PD-1/PD-L1 inhibitors in treatment of elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: Patients with advanced NSCLC ≥70 years old who received PD-1/PD-L1 inhibitors in our hospital were retrospectively analyzed. According to age, the patient were stratified as follows: 70-75 years old, 76-80 years old, and >80 years old. Kaplan-Meier method was used for survival analysis, and univariate and multivariate Cox proportional hazards regression models were used to analyze the correlation between different clinical characteristics and survival. RESULTS: A total of 58 elderly patients with advanced non-small cell cancer were enrolled in this study. Patients aged 70-75, 76-80, and >80 years old were 32, 19, and 7, respectively. For the all, median OS was 17.0 months, and PFS was 7.0 months. PFS and OS did not differ according to age (P = 0.396, 0.054, respectively). Univariate analysis showed that PS of 0-1, stage III, first-line therapy and irAEs were associated with longer PFS, and PS of 0-1, stage III, and first-line therapy were associated with longer OS. Multivariate analysis showed that patients with stage III had longer PFS. PFS and OS of patients with PS ≥ 2 were significantly shorter than those of patients with PS of 0-1. CONCLUSIONS: In the present real-world retrospective cohort, PD-1/PD-L1 inhibitors are effective and well tolerated in elderly patients with advanced NSCLC. Immunotherapy should be actively used as early as possible in older patients advanced NSCLC.

Preliminary research on the flavor substance and antioxidant capacity of beers produced with baking Qingke.

The addition of baked Qingke improves the flavor profile of beer. In this study, beer was brewed using Qingke baked at various temperatures. The beer produced with Qingke baked at 180 °C achieved the highest sensory score (40/50), an alcohol content of 6.92% (v/v), a total phenolic content of 446.42 mg/L, melanoidin concentration of 98.22 g/L, a color value of 10.88 EBC, and exhibited satisfactory antioxidant activity. Analysis of volatile compounds using HS-SPME-GC-MS revealed 48 compounds, of which esters accounted for 63% and alcohols accounted for 27% of the total content. The flavor profile of the beer varied across different baking temperatures. Pyrazines and aldehydes were predominantly present in samples baked at higher temperatures (T3, T4, and T5). Correlation analysis showed that the baking flavor in the beer was primarily correlated with 2, 5-dimethyl-pyrazine, trimethyl-pyrazine, phenylacetaldehyde, and ethyl 9-decenoate (R > 0.9).