Infectious endocarditis complicated with intracranial infected aneurysm rupture and sinus of valsalva aneurysm rupture.

BACKGROUND: Infectious endocarditis (IE) is an infectious disease caused by direct invasion of the heart valve, endocardium, or adjacent large artery endocardium by pathogenic microorganisms. Despite its relatively low incidence, it has a poor prognosis and a high mortality. Intracranial infectious aneurysms (IIA) and ruptured sinus of Valsalva aneurysm (RSVA) are rare complications of IE. CASE PRESENTATION: We report a young male patient with symptoms of respiratory tract infection, heart murmurs and other symptoms and signs. The patient also had kidney function impairment and poor response to symptomatic therapy. Blood culture was negative, but echocardiography was positive, which met the diagnostic criteria for infective endocarditis. Moreover, an echocardiography showed a ruptured sinus of Valsalva aneurysm with a ventricular septal defect. Finally, secondary rupture of an IIA with multiple organ damage led to a poor clinical outcome. CONCLUSION: Therefore, in the clinical setting, for young patients with unexplained fever, chest pain, or palpitations, we need to be highly vigilant, considering the possibility of infective endocarditis and promptly performing blood culture, echocardiography, cerebrovascular imaging and so on, in order to facilitate early proper diagnosis and treatment.

New drug combination regimen based on pharmacokinetic characteristics-Erdafitinib combined with sertraline or duloxetine.

The aim of this study is to investigate novel strategies for reducing adverse reactions caused by erdafitinib through a drug combination based on its pharmacokinetic characteristics. The spectrum and characterizations of drugs that can inhibit the metabolism of erdafitinib are examined both in vitro and in vivo. The efficacy of combination regimens are then evaluated using subcutaneous xenograft tumor models. The results demonstrated that sertraline and duloxetine, out of more than 100 screened drugs, inhibited the metabolism of erdafitinib through mixed and non-competitive inhibition, respectively. This inhibition primarily occurred via the CYP2C9 and CYP2D6 pathways. The primary alleles of CYP2C9 and CYP2D6 not only determine the metabolic characteristics of erdafitinib but also influence the strength of drug-drug interactions. Co-administration of sertraline or duloxetine with erdafitinib in rats and mice resulted in nearly a three-fold increase in the blood exposure of erdafitinib and its major metabolite M6. When sertraline or duloxetine was combined with 1/3 of the erdafitinib dosage, the anti-proliferative and pro-apoptotic effects on SNU-16 xenografts were comparable to those of the original full dose of erdafitinib. However, the combination regimen significantly mitigated hyperphosphatemia, retinal damage, intestinal villus damage, and gut microbiome dysbiosis. This study utilized pharmacokinetic methods to propose a new formulation of erdafitinib combined with sertraline or duloxetine. The findings suggest that this combination has potential for clinical co-administration based on a database analysis, thereby providing a novel strategy for anti-tumor treatment with fibroblast growth factor receptor (FGFR) inhibitors.

Association between processed red meat intake and cardiovascular risk factors in patients with type 2 diabetes: a cross-sectional study from China.

Aim: To explore the association between Processed red meat (PRM) consumption and cardiovascular risk factors in Chinese adults with type 2 diabetes mellitus (T2DM). Methods: Dietary survey, physical measurement, and blood biochemical examination were conducted on 316 patients with type 2 diabetes in Bengbu, China from May to July 2019. Possible confounding factors were identified by comparing between-group variability in the baseline table. To eliminate the effect of confounding factors, subgroup analysis was used to explore whether there were differences in the correlation between PRM intake status and the indicators in cardiovascular disease risk factors. A logistic regression model was used to analyze the association between PRM and the risk of abnormal levels of cardiovascular risk factors in T2DM patients. Restricted cubic spline plots were used to analyze the dose-response relationship between PRM intake and the indicators of cardiovascular disease risk factors. Results: A total of 316 subjects were included in the study, of whom 139 (44.0%) were male and 177 (56.0%) were female. In the multiplicative interaction, there was an effect modifier for smoking (Pinteraction = 0.033) on the association between PRM intake and the risk of substandard FPG level control; sex (Pinteraction = 0.035), smoking status (Pinteraction = 0.017), and alcohol consumption (Pinteraction = 0.046) had effect modifying effects on the association between PRM intake and risk of abnormal systolic blood pressure. Sex (Pinteraction = 0.045) had an effect modifier on the association of PRM intake status with the risk of diastolic blood pressure abnormality. In addition, age had an effect modifier on the association of PRM intake status with risk of abnormal triglyceride index (Pinteraction = 0.004) and risk of abnormal HDL index (Pinteraction = 0.018). After adjusting for potential confounding variables, logistic regression showed that the OR for substandard HbA1c control in patients in the highest PRM intake group, T3 (3.4 ~ 57.2 g/d), was 1.620-fold higher than in the lowest intake, i.e., the no-intake group, T1 (0.0 ~ 0.0 g/d; OR = 2.620; 95% CI 1.198 ~ 5.732; p = 0.016). Whereas the OR for abnormal control of systolic blood pressure levels was 1.025 times higher (OR = 2.025; 95% CI 1.033 ~ 3.968; p = 0.040) in patients in the PRM low intake group T2 (0.1 ~ 3.3 g/d) than in the non-intake group T1 (0.0 ~ 0.0 g/d), the OR for substandard control of systolic blood pressure in patients in the highest group T3 (3.4 ~ 57.2 g/d) was 1.166 times higher than in the no-intake group T1 (OR = 2.166; 95% CI 1.007 ~ 4.660; p = 0.048). The OR for abnormal TG levels in patients in the highest PRM intake group T3 (3.4 ~ 57.2 g/d) was 1.095 times higher than in the no-intake group T1 (OR = 2.095; 95% CI 1.076 ~ 4.078; p = 0.030). Restricted cubic spline plots presented a nonlinear dose-response relationship between PRM intake and risk of substandard HbA1c and SBP control (P nonlinear <0.05), and an atypical inverted U-shaped association between PRM intake and TC and LDL-C levels (P nonlinear <0.05). The strength of the associations between PRM intake and the control levels of FPG, DBP, HDL-C, and TG were not statistically significant (p > 0.05). Conclusion: PRM intake was generally low in patients with T2DM, but a nonlinear dose-response relationship between PRM intake and the risk of suboptimal control of HbA1c and SBP, with an atypical inverted U-shaped association with TC and LDL-C levels, was observed. Appropriate control of PRM intake may be important for tertiary prevention of T2DM and cardiovascular disease prevention. We need to better understand these relationships to promote improved cardiometabolism and global health.

Anatomical and functional evidence for renal autonomic innervation in normotensive and hypertensive rats.

Renal denervation (RDN) has been used for treating resistant hypertension. A few recent studies show vagal innervation of kidneys causing confusion. This study aimed to provide anatomical and functional evidence for renal autonomic innervation. Experiments were performed in male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Pseudorabies virus (PRV) in paraventricular nucleus and rostral ventrolateral medulla was prevented by bilateral RDN, but not subdiaphragmatic vagotomy. PRV did not appear in dorsal motor nucleus of vagus and nucleus tractus solitarii 72 h after renal injection of PRV. Adrenergic fibers were approximately 7 times more than cholinergic fibers in main renal artery (MRA) and its first (1RA) and second grade (2RA) branches. Adrenergic fibers in 1RA were more than these in MRA and 2RA. Tyrosine hydroxylase immunoreactivity in these arteries was higher in SHR than WKY. Norepinephrine (NE) increased, and α-receptor antagonist reduced vascular ring tension of renal arteries. The effect of NE was greater in 1RA and 2RA than MRA, which was prevented by α-receptor antagonist. Acetylcholine (ACh) or blockage of ß-receptors, M- or N-receptors had no significant effects on vascular ring tension and the effect of NE. Renal blood flow was reduced by electrical stimulation of renal nerves, but not affected by stimulation of subdiaphragmatic vagus. These results provide anatomical and functional evidence that kidneys are innervated and renal blood flow is regulated by renal sympathetic nerves rather than vagus. Renal vasoconstriction is regulated by NE and adrenergic fibers rather than ACh or cholinergic fibers in WKY and SHR.

Comparisons between ingestion, rejection, and egestion of microbeads by burrowing clams, Meretrix meretrix and Paphia undulata: Implications for health risk of shellfish consumption.

Two burrowing clam species, namely Meretrix meretrix and Paphia undulata, were offered two sizes (small: 45-53 µm, and large: 106-125 µm) of fluorescent red polyethylene microbeads, and the ingestion (number of MPs in the body tissue and faeces) and rejection (number of MPs in pseudofaeces) of MPs investigated. Overall, MP beads ingested were 36 % more than those rejected. There was also a significant interaction between the size and fate of MPs. For both species, significantly more small beads were ingested than rejected, but there was no difference for the large beads. P. undulata ingested more MPs than M. meretrix and both species could depurate all the ingested MPs in 72 h, although a longer time was needed for the former species. The results can provide guidance on seafood selection and pre-treatment to minimize the number of MPs ingested by humans.

A photovoltaic cell defect detection model capable of topological knowledge extraction.

As the global transition towards clean energy accelerates, the demand for the widespread adoption of solar energy continues to rise. However, traditional object detection models prove inadequate for handling photovoltaic cell electroluminescence (EL) images, which are characterized by high levels of noise. To address this challenge, we developed an advanced defect detection model specifically designed for photovoltaic cells, which integrates topological knowledge extraction. Our approach begins with the introduction of a multi-scale dynamic context-based feature extraction method, capable of generating static context by thoroughly capturing the local texture and structural information of multi-scale defects. This static context is then combined with dynamic context to produce fine-grained local features. Subsequently, we developed a centralized feature pyramid structure, enhanced by spatial semantics, which models the explicit visual center. This structure effectively elucidates the relationship between local and global features in defect images, thereby improving the representation of defect characteristics. Finally, we implemented a feature enhancement strategy grounded in spatial semantic knowledge extraction. This strategy uncovers potential correlations among defect targets by constructing a spatial semantic topology of features, mapping these features to a higher-order representation, and ultimately delivering precise defect detection results.

Risk factors for cancer-related cognitive impairment among individuals with lung cancer: a systematic review and meta-analysis.

OBJECTIVES: Cancer-related cognitive impairment (CRCI) exerts a negative impact on the quality of life in lung cancer survivors. Risk factors for CRCI in lung cancer patients remain unclear.This study aimed to identify risk factors for CRCI in lung cancer patients. METHODS: A comprehensive literature search was conducted across PubMed, CINAHL, Web of Science, Wanfang, VIP Database, Embase, and China National Knowledge Infrastructure (CNKI) from their inception until March 10, 2024. Studies were screened, data extracted, and quality assessed using the Agency for Healthcare Research and Quality and Newcastle-Ottawa Scale. Meta-analysis was performed using RevMan 5.4, assessing risk factors through odds ratios (OR) with 95% confidence intervals (CIs). RESULTS: The analysis was comprised of nine studies, including 1,305 patients. Seven studies were high quality, and two were moderate quality. Identified risk factors for CRCI in lung cancer patients included advanced age (OR = 3.51, 95%CI: 2.14-5.74, I2 = 0.0%), cranial irradiation (OR = 2.12, 95% CI: 1.39-3.22, I2 = 0.0%), anxiety (OR = 2.92, 95% CI: 1.65-5.25, I2 = 37%), and symptom cluster burden (OR = 4.85, 95% CI: 2.99-7.87, I2 = 0.0%). Physical activity (OR = 0.37, 95% CI; 0.23-0.58, I2 = 9.0%) was identified as a protective factor. CONCLUSION: Advanced age, cranial irradiation, anxiety, and symptom cluster burden are significant risk factors for CRCI, while physical activity serves as a protective factor. These insights provide healthcare professionals with an evidence-based framework for managing CRCI in lung cancer patients.

Utilizing biochars to stabilize mercury in contaminated floodplain sediment: Implications on mercury remediation.

Major weather events contribute to the mobility and remobilization of legacy mercury (Hg) contamination and sequestration within sediments. Remediation using biochar as a soil amendment is a useful technique to immobilize and decrease Hg toxicity. This study explored whether biochar application is effective at stabilizing labile mercury (LaHg) from floodplain sediment. Controlled mesocosms simulating contamination events and flooding conditions were conducted. Floodplain sediment, which experiences annual periodic flooding, was collected. Sediment was spiked with inorganic Hg, applied with different types of biochar, and experienced simulated flooding events. Four types of biochar, pure rice husk (RH), pure peanut hull (PH), sulfur-modified rice husk (SMRH), and sulfur-modified peanut hull (SMPH), were applied at 10 and 40 g/kg rates (i.e., RH 10, RH 40; PH 10, PH 40, SMRH 10, SMRH 40, SMPH 10, SMPH 40). Total Hg, methylmercury, and LaHg concentrations were analyzed by coupling with redox potential measurements. Results indicate that SMRH 10, PH 10, PH 40, SMPH 10, and SMPH 40 successfully remediate Hg by stabilizing and reducing LaHg species from floodplain sediment. However, a high Hg methylation potential was observed with unsulfated and sulfated peanut hulls (PH 10, PH 40, SMPH 10, and SMPH 40), as they tend to create a reducing microenvironment that favors sulfate reduction reactions. Additionally, sulfur-modified biochar tends to promote Hg methylation potential at high application rates (i.e., 40 g/kg). We thus recommend using SMRH at a relatively low application rate (SMRH 10) for the remediation of Hg from floodplain sediment.

Metabolic engineering of artificially modified transcription factor SmMYB36-VP16 for high-level production of tanshinones and phenolic acids.

Tanshinones and phenolic acids are the two main chemical constituents in Salvia miltiorrhiza, which are used clinically for the treatment of hypertension, coronary heart disease, atherosclerosis, and many other diseases, and have broad medicinal value. The efficient synthesis of the target products of these two metabolites in isolated plant tissues cannot be achieved without the regulation and optimization of metabolic pathways, and transcription factors play an important role as common regulatory elements in plant tissue metabolic engineering. However, most of the regulatory effects are specific to one class of metabolites, or an opposing regulation of two classes of metabolites exists. In this study, an artificially modified transcription factor, SmMYB36-VP16, was constructed to enhance tanshinones and phenolic acids in Salvia miltiorrhiza hair roots simultaneously. Further in combination with the elicitors dual-screening technique, by applying the optimal elicitors screened, the tanshinones content in the transgenic hairy roots of Salvia miltiorrhiza reached 6.44 mg/g DW, which was theoretically 6.08-fold that of the controls without any treatment, and the content of phenolic acids reached 141.03 mg/g DW, which was theoretically 5.05-fold that of the controls without any treatment. The combination of artificially modified transcriptional regulatory and elicitors dual-screening techniques has facilitated the ability of plant isolated tissue cell factories to produce targeted medicinal metabolites. This strategy could be applied to other species, laying the foundation for the production of potential natural products for the medicinal industry.

Effects of Fermentation with Kombucha Symbiotic Culture of Bacteria and Yeasts on Antioxidant Activities, Bioactive Compounds and Sensory Indicators of Rhodiola rosea and Salvia miltiorrhiza Beverages.

Kombucha is a well-known fermented beverage traditionally made from black tea infusion. Recent studies have focused on finding alternative materials to create novel kombucha beverages with various health benefits. In this study, we prepared and evaluated two novel kombucha beverages using Rhodiola rosea and Salvia miltiorrhiza as materials. The effects of fermentation with the residue of these plants on the kombucha were also investigated. The antioxidant activities, total phenolic contents, and concentrations of the bioactive compounds of the kombucha beverages were determined by the Trolox equivalent antioxidant capacity test, ferric-reducing antioxidant power test, Folin-Ciocalteu method, and high-performance liquid chromatography, respectively. The results revealed that the kombucha beverages made with Rhodiola rosea and Salvia miltiorrhiza had strong antioxidant capacities and abundant phenolic contents. Additionally, the kombucha fermented with Rhodiola rosea residue had higher FRAP, TEAC and TPC values than that fermented without residue. On the other hand, the Salvia miltiorrhiza kombucha fermented with residue had similar FRAP and TEAC values but lower TPC values compared to that fermented without residue. The correlation analysis showed that gallic acid, salidroside, and tyrosol were responsible for the antioxidant abilities and total phenolic contents of the Rhodiola rosea kombucha, and salvianolic acid A and salvianolic acid B contributed to the antioxidant abilities of the Salvia miltiorrhiza kombucha. Furthermore, the kombucha fermented with Rhodiola rosea residue had the highest sensory scores among the kombucha beverages studied. These findings suggest that Rhodiola rosea and Salvia miltiorrhiza are suitable for making novel kombucha beverages with strong antioxidant abilities and abundant phenolic contents, which can be used in preventing and managing oxidative stress-related diseases.

Cochlear reimplantation outcomes over 20 years: Expertise in reimplantation surgery and auditory-speech rehabilitation.

OBJECTIVES: The aim of this study was to present an institution's experience with cochlear reimplantation (CRI), to assess surgical challenges and post-operative outcomes and to increase the success rate of CRI. STUDY DESIGN: Retrospective single-institution study. SETTING: Tertiary medical center. METHODS: We retrospectively evaluated data from 76 reimplantation cases treated in a tertiary center between 2001 and 2022. Clinical features including etiology of hearing loss, type of failure, surgical issues, and auditory speech performance were analyzed. Categorical Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) scores were used to evaluate pre- and post-CRI outcomes. RESULTS: The CRI population comprises of 7 patients from our institute,69 referred patients from other centers. Device failure was the most common reason (68/76, 89.5 %) for CRI; in addition, there were 7 medical failures and 1 had both soft device failure. Medical failures included flap rupture and device extrusion, magnet migration, auditory neuropathy, leukoencephalopathy, foreign-body residue and meningitis. In 21/76 patients, the electrode technology was upgraded. The mean time to failure was 0.58-13 years, with a mean of 4.97 years. The mean (± SD) CAP and SIR scores before and after CRI were 5.2 ± 1.2 versus 5.5 ± 1.1 and 3.4 ± 1.1 versus 3.5 ± 1.1, respectively. Performance was poor in six patients with severe cochlear malformation, auditory nerve dysplasia, leukoencephalopathy, and epilepsy. CONCLUSION: CRI surgery is a challenging but relatively safe procedure, and most reimplanted patients experience favorable postoperative outcomes. Medical complications and intracochlear damage are the main causes of poor postoperative results. Therefore, adequate preoperative preparation and atraumatic CRI should be carried out for optimal results.

Interaction between microalgae and phycosphere bacteria in a binary cultivation system-based dairy farm wastewater treatment.

The combination of microalgal culture and wastewater treatment is an emerging topic. This study investigated the use of different microalgae to treat different types of dairy farm wastewater. The results showed that the removal of ammonia nitrogen and total phosphorus by mixed microalgae was over 99% and 80%, respectively. The highest production of protein in biomass and extracellular polymeric substances was observed in high-concentration wastewater. In the phycosphere, the abundance of Proteobacteria and Cyanobacteria increased, while that of Bacteroidota decreased. Phycosphere bacteria were strongly correlated with microalgal growth and the composition of extracellular polymeric substances, especially with bound extracellular polymeric substances relative to soluble extracellular polymeric substances. Genes associated with photosynthesis and respiration in phycosphere bacteria were upregulated, contributing to the material exchange capacity in the microalgal-bacterial systems. The interaction between microalgae and phycosphere bacteria thus represents the core of the binary cultivation system-based wastewater treatment and requires further investigation.

The receptor VLDLR binds Eastern Equine Encephalitis virus through multiple distinct modes.

Eastern Equine Encephalitis virus (EEEV) is an alphavirus that can cause severe diseases in infected humans. The very low-density lipoprotein receptor (VLDLR) was recently identified as a receptor of EEEV. Herein, we performed cryo-electron microscopy structural and biochemistry studies on the specific interactions between EEEV and VLDLR. Our results show that VLDLR binds EEEV at three different sites A, B and C through its membrane-distal LDLR class A (LA) repeats. Site A is located in the cleft in between the E1-E2 heterodimers. Site B is located near the connecting ß ribbon of E2 and is in proximity to site A, while site C is on the domain B of E2. The binding of VLDLR LAs to EEEV is in complex modes, including the LA1-2 and LA3-5 mediated two major modes. Disruption of the LA1-2 mediated binding significantly affect the cell attachment of EEEV. However, the mutation W132G of VLDLR impairs the binding of LA3, drives the switch of the binding modes, and significantly enhances the attachment of EEEV to the cell. The W132G variant of VLDLR could be identified in human genome and SNP sequences, implying that people with similar mutations in VLDLR may be highly susceptible to EEEV infection.

Drug-induced enzyme activity inhibition and CYP3A4 genetic polymorphism significantly shape the metabolic characteristics of furmonertinib.

This study aimed to elucidate the impact of variations in liver enzyme activity, particularly CYP3A4, on the metabolism of furmonertinib. An in vitro enzyme incubation system was established for furmonertinib using liver microsomes and recombinant CYP3A4 baculosomes, with analytes detected by LC-MS/MS. The pharmacokinetic characteristics of furmonertinib were studied in vivo using Sprague-Dawley rats. It was found that telmisartan significantly inhibited the metabolism of furmonertinib, as demonstrated by a significant increase in the AUC of furmonertinib when co-administered with telmisartan, compared to the furmonertinib-alone group. Mechanistically, it was noncompetitive in rat liver microsomes, while it was mixed competitive and noncompetitive in human liver microsomes and CYP3A4. Considering the genetic polymorphism of CYP3A4, the study further investigated its effect on the kinetics of furmonertinib. The results showed that compared to CYP3A4.1, CYP3A4.29 had significantly increased activity in catalyzing furmonertinib, whereas CYP3A4.7, 9, 10, 12, 13, 14, 18, 23, 33, and 34 showed markedly decreased activity. The inhibitory activity of telmisartan varied in CYP3A4.1 and CYP3A4.18, with IC50 values of 8.56 ± 0.90 µM and 27.48 ± 3.52 µM, respectively. The key loci affecting the inhibitory effect were identified as ARG105, ILE301, ALA370, and LEU373. Collectively, these data would provide a reference for the quantitative application of furmonertinib.

Engineering a Bifunctional Smart Nanoplatform Integrating Nanozyme Activity and Self-Assembly for Kidney Cancer Diagnosis and Classification.

Accurate diagnosis and classification of kidney cancer are crucial for high-quality healthcare services. However, the current diagnostic platforms remain challenges in the rapid and accurate analysis of large-scale clinical biosamples. Herein, we fabricated a bifunctional smart nanoplatform based on tannic acid-modified gold nanoflowers (TA@AuNFs), integrating nanozyme catalysis for colorimetric sensing and self-assembled nanoarray-assisted LDI-MS analysis. The TA@AuNFs presented peroxidase (POD)- and glucose oxidase-like activity owing to the abundant galloyl residues on the surface of AuNFs. Combined with the colorimetric assay, the TA@AuNF-based sensing nanoplatform was used to directly detect glucose in serum for kidney tumor diagnosis. On the other hand, TA@AuNFs could self-assemble into closely packed and homogeneous two-dimensional (2D) nanoarrays at liquid-liquid interfaces by using Fe3+ as a mediator. The self-assembled TA@AuNFs (SA-TA@AuNFs) arrays were applied to assist the LDI-MS analysis of metabolites, exhibiting high ionization efficiency and excellent MS signal reproducibility. Based on the SA-TA@AuNF array-assisted LDI-MS platform, we successfully extracted metabolic fingerprints from urine samples, achieving early-stage diagnosis of kidney tumor, subtype classification, and discrimination of benign from malignant tumors. Taken together, our developed TA@AuNF-based bifunctional smart nanoplatform showed distinguished potential in clinical disease diagnosis, point-of-care testing, and biomarker discovery.

Seasonal Sulfur Redox Cycling in Two Constructed Wetlands with Insight on How They Age.

Long-term metal remediation in wetland treatment systems (WTSs) involves facilitating dissimilatory sulfate reduction to produce sulfide and mineralize metals in deep sediments. We evaluated seasonal sulfur cycling in two constructed wetlands (Maintained WTS constructed in 2007, and the Unmaintained WTS constructed in 2000) on the Savannah River Site in Aiken, South Carolina, USA. Significant interactions in sulfide concentration were observed between sediment depth, season, and wetland (F = 4.64, df = 11, P = 3.28 × 10 - 5). In the Maintained WTS, dissimilatory sulfate reduction dominated the surface sediments during the warm season (0-2 cm depth, t=-2.66, P = 9.70 × 10 - 3), unlike the Unmaintained system. Sulfate concentrations in pore waters increased in the warm season (F = 7.84, df = 1, P = 6.50 × 10 - 3), contrary to expectations. Sulfur limitation in the Unmaintained WTS during the warm season correlated with increased sulfur assimilation in giant bulrush. Lower sulfide concentrations in surface sediments of the Unmaintained WTS illustrated aging effects. The Maintained WTS shows potential for managing erosion, pH reduction, and sulfur limitation observed in the older Unmaintained WTS.

Utilizing Macrophages Missile for Sulfate-Based Nanomedicine Delivery in Lung Cancer Therapy.

Nanomaterial-based drug delivery systems are susceptible to premature drug leakage and systemic toxicity due to lack of specific targeting, and live-cell drug delivery is also prone to be restricted by drug carrier-cell interactions. Here, a method is established to adsorb drug-loaded nanomaterials externally to the live cells, which reduces cytotoxicity caused by drug uptake and improves the bioactivity of the carrier cells and drug release at the lesion site. It was found that polyphenols act like "double-sided tape" to bridge metal-organic framework (MOF) nanoparticles with live macrophages (Mφ), attaching MOFs to the Mφ surface and minimizing intracellular uptake, with no negative effect on cell proliferation. On this basis, a "macrophage missile" with peroxymonosulfate (PMS)-loaded MOF nanoparticles on the cell surface was constructed. As a "propellant", the Mφ, in which bioactivity is preserved, can selectively identify and target tumor cells, precisely bringing nanomedicines to the lesion. MOF nanoparticles are used to load and catalyze PMS, which acts as an exogenous source of reactive oxygen species, showing higher efficacy and lower toxicity in an oxygen-independent manner. The primary study results demonstrate that this innovative combination of biology and nanomaterials remarkably enhances tumor targeting and therapeutic efficacy while reducing systemic side effects. This approach is expected to provide a more effective and safer treatment for lung cancer and holds promise for broader applications in other cancer therapies.

Serum and Urine Metabolic Fingerprints Characterize Renal Cell Carcinoma for Classification, Early Diagnosis, and Prognosis.

Renal cell carcinoma (RCC) is a substantial pathology of the urinary system with a growing prevalence rate. However, current clinical methods have limitations for managing RCC due to the heterogeneity manifestations of the disease. Metabolic analyses are regarded as a preferred noninvasive approach in clinics, which can substantially benefit the characterization of RCC. This study constructs a nanoparticle-enhanced laser desorption ionization mass spectrometry (NELDI MS) to analyze metabolic fingerprints of renal tumors (n = 456) and healthy controls (n = 200). The classification models yielded the areas under curves (AUC) of 0.938 (95% confidence interval (CI), 0.884-0.967) for distinguishing renal tumors from healthy controls, 0.850 for differentiating malignant from benign tumors (95% CI, 0.821-0.915), and 0.925-0.932 for classifying subtypes of RCC (95% CI, 0.821-0.915). For the early stage of RCC subtypes, the averaged diagnostic sensitivity of 90.5% and specificity of 91.3% in the test set is achieved. Metabolic biomarkers are identified as the potential indicator for subtype diagnosis (p < 0.05). To validate the prognostic performance, a predictive model for RCC participants and achieve the prediction of disease (p = 0.003) is constructed. The study provides a promising prospect for applying metabolic analytical tools for RCC characterization.

Morphological Brain Networks of White Matter: Mapping, Evaluation, Characterization, and Application.

Although white matter (WM) accounts for nearly half of adult brain, its wiring diagram is largely unknown. Here, an approach is developed to construct WM networks by estimating interregional morphological similarity based on structural magnetic resonance imaging. It is found that morphological WM networks showed nontrivial topology, presented good-to-excellent test-retest reliability, accounted for phenotypic interindividual differences in cognition, and are under genetic control. Through integration with multimodal and multiscale data, it is further showed that morphological WM networks are able to predict the patterns of hamodynamic coherence, metabolic synchronization, gene co-expression, and chemoarchitectonic covariance, and associated with structural connectivity. Moreover, the prediction followed WM functional connectomic hierarchy for the hamodynamic coherence, is related to genes enriched in the forebrain neuron development and differentiation for the gene co-expression, and is associated with serotonergic system-related receptors and transporters for the chemoarchitectonic covariance. Finally, applying this approach to multiple sclerosis and neuromyelitis optica spectrum disorders, it is found that both diseases exhibited morphological dysconnectivity, which are correlated with clinical variables of patients and are able to diagnose and differentiate the diseases. Altogether, these findings indicate that morphological WM networks provide a reliable and biologically meaningful means to explore WM architecture in health and disease.

Immunomodulatory Effects of Yu-Ping-Feng Formula on Primary Sjögren's Syndrome: Interrogating the T Cell Response.

Ethnopharmacological treatments have shown beneficial effects in the clinical practice of autoimmune disorders. However, the underlying mechanism of immunomodulatory effects remains challenging, given the complicate composition of herbal medicines. Here, we developed an immunological approach to interrogate the T helper cell response. Through data mining we hypothesized that Chinese medicine formula, Yu-Ping-Feng (YPF) might be a promising candidate for treating primary Sjögren's syndrome (pSS), a common autoimmune disease manifested by exocrine gland dysfunction. We took advantage of a mouse model of experimental Sjögren's syndrome (ESS) that we previously established for YPF formula treatment. YPF therapy ameliorated the ESS pathology in mice with active disease, showing improved salivary function and decreased serum levels of autoantibodies. Phenotypic analysis suggested that both effector T and B cells were significantly suppressed. Using co-culture assay and adoptive transfer models, we demonstrated that YPF formula directly restrained effector/memory T cell expansion and differentiation into Th17 and T follicular helper (Tfh) cells, the key subsets in ESS pathogenesis. Importantly, we recruited 20 pSS patients and conducted a pilot study of 8-week therapy of YPF formula. YPF treatment effectively improved fatigue symptoms, exocrine gland functions and reduced serum IgG/IgA levels, while effector T and B cell subsets were significantly decreased. There was a trend of reduction on disease activity, but not statistically significant. Together, our findings suggested a novel approach to assess the immunomodulatory effects of YPF formula, which may be favorable for patients with autoimmune disorders.