Improved Lignin Conversion to High-Value Aromatic Monomers through Phase Junction CdS with Coexposed Hexagonal (100) and Cubic (220) Facets.

Photocatalysis has the potential for lignin valorization to generate functionalized aromatic monomers, but its application has been limited by the slow conversion rate and the low selectivity to desirable aromatic products. In this work, we designed the phase junction CdS with coexposed hexagonal (100) and cubic (220) facets to improve the photogenerated charge carriers' transfer efficiency from (100) facet to (220) facet and the hydrogen transfer efficiency for an enhanced conversion rate of lignin to aromatic monomers. Water is found as a sufficient external hydrogen supplier to increase the yields of aromatic monomers. These innovative designs in the reaction system promoted complete conversion of PP-ol to around 94% of aromatic monomers after 1 h of visible light irradiation, which shows the highest reaction rate and selectivity of target products in comparison with previous works. PP-one is a byproduct from the overoxidation of PP-ol and is usually difficult to be further cleaved to acetophenone and phenol as the desirable aromatic monomers. TEA was first identified in this study as a sacrificial electron donor, a hydrogen source, and a mediator to enhance the cleavage of the Cß-O bonds in PP-one. With the assistance of TEA, PP-one can be completely cleaved to desirable aromatic monomer products, and the reaction time is reduced from several hours to 10 min of visible light irradiation.

Chrysanthemum morifolium Ramat extract and probiotics combination ameliorates metabolic disorders through regulating gut microbiota and PPARα subcellular localization.

BACKGROUND: Chrysanthemum morifolium Ramat, a traditional Chinese medicine, has the effects on liver clearing, vision improving, and anti-inflammation. C. morifolium and probiotics have been individually studied for their beneficial effects on metabolic diseases. However, the underlying molecular mechanisms were not completely elucidated. This study aims to elucidate the potential molecular mechanisms of C. morifolium and probiotics combination (CP) on alleviating nonalcoholic fatty liver disease (NAFLD) and the dysregulation of glucose metabolism in high-fat diet (HFD)-fed mice. METHODS: The therapeutic effect of CP on metabolism was evaluated by liver histology and serum biochemical analysis, as well as glucose tolerance test. The impact of CP on gut microbiota was analyzed by 16S rRNA sequencing and fecal microbiota transplantation. Hepatic transcriptomic analysis was performed with the key genes and proteins validated by RT-qPCR and western blotting. In addition, whole body Pparα knockout (Pparα-/-) mice were used to confirm the CP-mediated pathway. RESULTS: CP supplementation ameliorated metabolic disorders by reducing body weight and hepatic steatosis, and improving glucose intolerance and insulin resistance in HFD fed mice. CP intervention mitigated the HFD-induced gut microbiota dysbiosis, which contributed at least in part, to the beneficial effect of improving glucose metabolism. In addition, hepatic transcriptomic analysis showed that CP modulated the expression of genes associated with lipid metabolism. CP downregulated the mRNA level of lipid droplet-binding proteins, such as Cidea and Cidec in the liver, leading to more substrates for fatty acid oxidation (FAO). Meanwhile, the expression of CPT1α, the rate-limiting enzyme of FAO, was significantly increased upon CP treatment. Mechanistically, though CP didn't affect the total PPARα level, it promoted the nuclear localization of PPARα, which contributed to the reduced expression of Cidea and Cidec, and increased expression of CPT1α, leading to activated FAO. Moreover, whole body PPARα deficiency abolished the anti-NAFLD effect of CP, suggesting the importance of PPARα in CP-mediated beneficial effect. CONCLUSION: This study revealed the hypoglycemic and hepatoprotective effect of CP by regulating gut microbiota composition and PPARα subcellular localization, highlighting its potential for therapeutic candidate for metabolic disorders.

Nicotinamide Mononucleotide Supplementation Alleviates Doxorubicin-Induced Multi-Organ Fibrosis.

Doxorubicin (DOX) is a potent chemotherapeutic agent known for its multi-organ toxicity, especially in the heart, which limits its clinical application. The toxic side effects of DOX, including DNA damage, oxidative stress, mitochondrial dysfunction and cell apoptosis, are intricately linked to the involvement of nicotinamide adenine dinucleotide (NAD+). To assess the effectiveness of the NAD+ precursor nicotinamide mononucleotide (NMN) in counteracting the multi-organ toxicity of DOX, a mouse model was established through DOX administration, which led to significant reductions in NAD+ in tissues with evident injury, including the heart, liver and lungs. NMN treatment alleviated both multi-organ fibrosis and mortality in mice. Mechanistically, tissue fibrosis, macrophage infiltration and DOX-related cellular damage, which are potentially implicated in the development of multi-organ fibrosis, could be attenuated by NAD+ restoration. Our findings provide compelling evidence for the benefits of NMN supplementation in mitigating the adverse effects of chemotherapeutic drugs on multiple organs.

Isolation of Extracellular Outer Membrane Vesicles (OMVs) from Escherichia coli Using EVscore47 Beads.

Outer membrane vesicles (OMVs) are attractive for biomedical applications based on their intrinsic properties in relation to bacteria and vesicles. However, their widespread use is hampered by low yields and purities. In this study, EVscore47 multifunctional chromatography microspheres were synthesized and used to efficiently isolate functional OMVs from Escherichia coli. Through this technology, OMV loss can be kept to a minimum, and OMVs can be harvested using EVscore47 at 11-fold higher yields and ~13-fold higher purity than those achieved by means of ultracentrifugation. Based on the results presented here, we propose a novel EVscore47-based isolation of OMVs that is fast and scalable.

Current status and influencing factors of family resilience in families of children with epilepsy: a cross-sectional study.

Purpose: The study was designed to describe the level of family resilience and identify the protective factors and vulnerability factors of family resilience in families of children with epilepsy. So as to provide theoretical guidance for implementing intervention programs to promote family resilience. Methods: From November 2020 to July 2021, 258 parents of children with epilepsy were investigated using a convenience sampling method. The questionnaire included demographic data, Chinese-Family Resilience Assessment Scale, Social Support Rating Scale, and the Beck Depression Inventory. SPSS25.0 was used for descriptive statistical analysis, univariate analysis, and multivariate linear regression analysis. Results: In this study, two hundred and fifty-eight primary caregivers completed the paper questionnaires. The total score of family resilience was (134.97 ± 16.57), which was above the medium level. Multiple linear regression analysis revealed that subjective support (ß=0.327, P<0.001), comorbidity (ß=0.181, P<0.05), objective support (ß=0.117, P<0.05), and parental depression (ß=-0.158, P<0.05) were significantly related to family resilience. These variables contribute 31.7% of the variance in family resilience (F=18.07, P< 0.001). Conclusion: The families of children with epilepsy presented appropriate resilience after the children were diagnosed with epilepsy. Family resilience was correlated with multiple factors, subjective and objective support could be protective factors, comorbidity and parental depression could be vulnerability factors of family resilience. Therefore, future psychosocial interventions could focus on enhancing subjective support and objective support, reducing parental depression, and screening for epilepsy comorbidity to promote the family resilience of children with epilepsy.

Astragalus polysaccharides attenuate chemotherapy-induced immune injury by modulating gut microbiota and polyunsaturated fatty acid metabolism.

BACKGROUND: The damage of chemotherapy drugs to immune function and intestinal mucosa is a common side effect during chemotherapy. Astragalus polysaccharides (APS) exhibit immunomodulatory properties and are recognized for preserving the integrity of the human intestinal barrier. Nevertheless, their application and mechanisms of action in chemotherapy-induced immune damage and intestinal barrier disruption remain insufficiently explored. PURPOSE: This study delved into investigating how APS mitigates chemotherapy-induced immune dysfunction and intestinal mucosal injury, while also providing deeper insights into the underlying mechanisms. METHODS: In a chemotherapy mice model induced by 5-fluorouracil (5-Fu), the assessment of APS's efficacy encompassed evaluations of immune organ weight, body weight, colon length, and histopathology. The regulation of different immune cells in spleen was detected by flow cytometry. 16S rRNA gene sequencings, ex vivo microbiome assay, fecal microbiota transplantation (FMT), and targeted metabolomics analysis were applied to explore the mechanisms of APS effected on chemotherapy-induced mice. RESULTS: APS ameliorated chemotherapy-induced damage to immune organs and regulated immune cell differentiation disorders, including CD4+T, CD8+T, CD19+B, F4/80+CD11B+ macrophages. APS also alleviated colon shortening and upregulated the expression of intestinal barrier proteins. Furthermore, APS significantly restored structure of gut microbiota following chemotherapy intervention. Ex vivo microbiome assays further demonstrated the capacity of APS to improve 5-Fu-induced microbiota growth inhibition and compositional change. FMT demonstrated that the regulation of gut microbiota by APS could promote the recovery of immune functions and alleviate shortening of the colon length. Remarkably, APS significantly ameliorated the imbalance of linoleic acid (LA) and α-linolenic acid in polyunsaturated fatty acid (PUFA) metabolism. Further in vitro experiments showed that LA could promote splenic lymphocyte proliferation. In addition, both LA and DGLA down-regulated the secretion of NO and partially up-regulated the percentage of F4/80+CD11B+CD206+ cells. CONCLUSION: APS can effectively ameliorate chemotherapy-induced immune damage and intestinal mucosal disruption by regulating the composition of the gut microbiota and further restoring PUFA metabolism. These findings indicate that APS can serve as an adjuvant to improve the side effects such as intestinal and immune damage caused by chemotherapy.

Upregulation of CYR61 by TGF-ß and YAP signaling exerts a counter-suppression of hepatocellular carcinoma.

Transforming growth factor-ß (TGF-ß) and Hippo signaling are two critical pathways engaged in cancer progression by regulating both oncogenes and tumor suppressors, yet how the two pathways coordinately exert their functions in the development of hepatocellular carcinoma (HCC) remains elusive. In this study, we firstly conducted an integrated analysis of public liver cancer databases and our experimental TGF-ß target genes, identifying CYR61 as a pivotal candidate gene relating to HCC development. The expression of CYR61 is downregulated in clinical HCC tissues and cell lines than that in the normal counterparts. Evidence revealed that CYR61 is a direct target gene of TGF-ß in liver cancer cells. In addition, TGF-ß-stimulated Smad2/3 and the Hippo pathway downstream effectors YAP and TEAD4 can form a protein complex on the promoter of CYR61, thereby activating the promoter activity and stimulating CYR61 gene transcription in a collaborative manner. Functionally, depletion of CYR61 enhanced TGF-ß- or YAP-mediated growth and migration of liver cancer cells. Consistently, ectopic expression of CYR61 was capable of impeding TGF-ß- or YAP-induced malignant transformation of HCC cells in vitro and attenuating HCC xenograft growth in nude mice. Finally, transcriptomic analysis indicates that CYR61 can elicit an antitumor program in liver cancer cells. Together, these results add new evidence for the crosstalk between TGF-ß and Hippo signaling and unveil an important tumor suppressor function of CYR61 in liver cancer.

Adjuvant sintilimab in resected high-risk hepatocellular carcinoma: a randomized, controlled, phase 2 trial.

Hepatocellular carcinoma (HCC), particularly when accompanied by microvascular invasion (MVI), has a markedly high risk of recurrence after liver resection. Adjuvant immunotherapy is considered a promising avenue. This multicenter, open-label, randomized, controlled, phase 2 trial was conducted at six hospitals in China to assess the efficacy and safety of adjuvant sintilimab, a programmed cell death protein 1 inhibitor, in these patients. Eligible patients with HCC with MVI were randomized (1:1) into the sintilimab or active surveillance group. The sintilimab group received intravenous injections every 3 weeks for a total of eight cycles. The primary endpoint was recurrence-free survival (RFS) in the intention-to-treat population. Key secondary endpoints included overall survival (OS) and safety. From September 1, 2020, to April 23, 2022, a total of 198 eligible patients were randomly allocated to receive adjuvant sintilimab (n = 99) or undergo active surveillance (n = 99). After a median follow-up of 23.3 months, the trial met the prespecified endpoints. Sintilimab significantly prolonged RFS compared to active surveillance (median RFS, 27.7 versus 15.5 months; hazard ratio 0.534, 95% confidence interval 0.360-0.792; P = 0.002). Further follow-up is needed to confirm the difference in OS. In the sintilimab group, 12.4% of patients experienced grade 3 or 4 treatment-related adverse events, the most common of which were elevated alanine aminotransferase levels (5.2%) and anemia (4.1%). These findings support the potential of immune checkpoint inhibitors as effective adjuvant therapy for these high-risk patients. Chinese Clinical Trial Registry identifier: ChiCTR2000037655 .

Combination eravacycline therapy for ventilator-associated pneumonia due to carbapenem-resistant Acinetobacter baumannii in patients with COVID-19: A case series.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia is associated with poor clinical outcomes and increased mortality. Clinical data regarding the optimal treatment of CRAB is limited, and combination therapy is often preferred. Eravacycline has demonstrated in-vitro activity against A. baumannii and has been considered for the treatment of pulmonary infections caused by CRAB. OBJECTIVE: The objective of this case series was to describe clinical outcomes associated with eravacycline when utilized as part of a combination regimen for the treatment of CRAB pneumonia at a county hospital. METHODS: A retrospective chart review was conducted from April 1, 2020, to October 1, 2020, which included hospitalized patients ≥18 years of age, diagnosed with coronavirus disease 2019 (COVID-19), with a sputum culture positive for CRAB, and receipt of at least one dose of eravacycline. The primary outcome studied was clinical resolution of CRAB pneumonia. A key secondary outcome was microbiological resolution. RESULTS: A total of 24 patients received combination eravacycline therapy for a median of 10.5 days. Overall, 17 (71%) patients demonstrated clinical resolution of CRAB pneumonia. Repeat sputum cultures post-treatment were collected in 17 (71%) patients, of which 12 (71%) achieved microbiological resolution. No adverse events attributable to eravacycline were identified. CONCLUSION: With limited viable salvage treatment options, combination eravacycline therapy showed favorable microbiological and clinical outcomes in patients with CRAB pneumonia. In light of this, eravacycline could be considered as a potential treatment option when designing CRAB pneumonia salvage therapy regimens.

Comparison of the MeltPro TB assay and whole-genome sequencing assay for rapid molecular diagnosis of drug resistant tuberculosis in guangdong province.

BACKGROUND: Rifampicin (RIF) and multidrug-resistant tuberculosis (TB) are major public health threats. As conventional phenotypic drug susceptibility testing requires two-eight weeks, molecular diagnostic assays are widely used to determine drug resistance. METHODS: Clinical Mycobacterium tuberculosis isolates with consistent drug susceptibility results, tested using microbroth dilution and proportion methods in Löwenstein-Jensen medium from patients with TB in Guangdong province were utilized to evaluate MeltPro TB and whole-genome sequencing (WGS) assays in detecting resistance to RIF, isoniazid (INH), ethambutol (EMB), fluoroquinolones (FQ), and streptomycin (SM). Solid phenotypic drug susceptibility testing was used as the gold standard to evaluate the detection capacity of MeltPro TB on clinical sputum samples of patients with TB. RESULTS: Similar to WGS, MeltPro TB successfully detected RIF, INH, and SM resistance with sensitivities of 86.3, 84.8, and 86.6 %, respectively. However, the resistant isolate detection rates were only 58.1 and 69.6 % for EMB and FQ-resistant strains. For clinical specimens, MeltPro TB still showed good detectable rates of RIF and INH resistance, with sensitivities of 82.4 % and 95.2 %, respectively. Detectable rates of FQ and EMB resistance were low: 77.8 % and 35.3 %, respectively. CONCLUSIONS: MeltPro TB can detect known DNA mutations associated with drug resistance in Mycobacterium tuberculosis strains with comparable efficacy to WGS. For FQ and EMB resistance testing, MeltPro TB requires optimization and is unsuitable for general use. MeltPro TB can be used for diagnosis of RIF and multidrug-resistant tuberculosis to rapidly initiate appropriate anti-TB drug therapy.

Disrupted topological organization of the default mode network in mild cognitive impairment with subsyndromal depression: A graph theoretical analysis.

AIMS: Subsyndromal depression (SSD) is common in mild cognitive impairment (MCI). However, the neural mechanisms underlying MCI with SSD (MCID) are unclear. The default mode network (DMN) is associated with cognitive processes and depressive symptoms. Therefore, we aimed to explore the topological organization of the DMN in patients with MCID. METHODS: Forty-two MCID patients, 34 MCI patients without SSD (MCIND), and 36 matched healthy controls (HCs) were enrolled. The resting-state functional connectivity of the DMN of the participants was analyzed using a graph theoretical approach. Correlation analyses of network topological metrics, depressive symptoms, and cognitive function were conducted. Moreover, support vector machine (SVM) models were constructed based on topological metrics to distinguish MCID from MCIND. Finally, we used 10 repeats of 5-fold cross-validation for performance verification. RESULTS: We found that the global efficiency and nodal efficiency of the left anterior medial prefrontal cortex (aMPFC) of the MCID group were significantly lower than the MCIND group. Moreover, small-worldness and global efficiency were negatively correlated with depressive symptoms in MCID, and the nodal efficiency of the left lateral temporal cortex and left aMPFC was positively correlated with cognitive function in MCID. In cross-validation, the SVM model had an accuracy of 0.83 [95% CI 0.79-0.87], a sensitivity of 0.88 [95% CI 0.86-0.90], a specificity of 0.75 [95% CI 0.72-0.78] and an area under the curve of 0.88 [95% CI 0.85-0.91]. CONCLUSIONS: The coexistence of MCI and SSD was associated with the greatest disrupted topological organization of the DMN. The network topological metrics could identify MCID and serve as biomarkers of different clinical phenotypic presentations of MCI.

EspB and HtpG interact with the type III-A CRISPR/Cas system of Mycobacterium tuberculosis.

Introduction: Mycobacterium tuberculosis (MTB) has a type III-A clustered regularly interspaced short palindromic repeat/CRISPR-associated protein (CRISPR/Cas) system consisting of a Csm1-5 and CRISPR RNA (crRNA) complex involved in the defense against invading nucleic acids. However, CRISPR/Cas system in the MTB still is clearly unknown and needs to be further explored. Methods: In our work, two non-Cas system proteins EspB and HtpG protein were found and identified by LC-MS/MS. The effect of EspB and HtpG on Type III-A CRISPR/Cas System of M. tuberculosis was examined by using Plasmid interference assay and Co-immunoprecipitation analyses. We explored that EspB could interact with the crRNA RNP complex, but HtpG could inhibit the accumulation of the MTB Csm proteins and defense the mechanism of CRISPR/Cas system. Results: The proteins ESAT-6 secretion system-1(Esx-1) secreted protein B (EspB) and high-temperature protein G (HtpG), which were not previously associated with CRISPR/Cas systems, are involved in mycobacterial CRISPR/Cas systems with distinct functions. Conclusion: EspB is a novel crRNA-binding protein that interacts directly with the MTB crRNP complex. Meanwhile, HtpG influences the accumulation of MTB Csm proteins and EspB and interferes with the defense mechanism of the crRNP complex against foreign DNA in vivo. Thereby, our study not only leads to developing more precise clinical diagnostic tool to quickly detect for MTB infection, but also knows these proteins merits for TB biomarkers/vaccine candidates.

A new variant of the colistin resistance gene MCR-1 with co-resistance to ß-lactam antibiotics reveals a potential novel antimicrobial peptide.

The emerging and global spread of a novel plasmid-mediated colistin resistance gene, mcr-1, threatens human health. Expression of the MCR-1 protein affects bacterial fitness and this cost correlates with lipid A perturbation. However, the exact molecular mechanism remains unclear. Here, we identified the MCR-1 M6 variant carrying two-point mutations that conferred co-resistance to ß-lactam antibiotics. Compared to wild-type (WT) MCR-1, this variant caused severe disturbance in lipid A, resulting in up-regulation of L, D-transpeptidases (LDTs) pathway, which explains co-resistance to ß-lactams. Moreover, we show that a lipid A loading pocket is localized at the linker domain of MCR-1 where these 2 mutations are located. This pocket governs colistin resistance and bacterial membrane permeability, and the mutated pocket in M6 enhances the binding affinity towards lipid A. Based on this new information, we also designed synthetic peptides derived from M6 that exhibit broad-spectrum antimicrobial activity, exposing a potential vulnerability that could be exploited for future antimicrobial drug design.

A study on community older people's willingness to use smart home-an extended technology acceptance model with intergenerational relationships.

Introduction: Despite the potential of smart home technology to promote sustainable lifestyles, the adoption rate among older adults remains relatively low. This study aims to investigate the influence of intergenerational relationships on the acceptance of smart home services among seniors. Methods: A survey was conducted among 298 older adults in China, and data were analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). Ten predictor variables were examined to assess their impact on the willingness to use smart home services. Results: Intergenerational relationships significantly influenced the utilization of smart home services among older adults. Specifically, intergenerational instrumental support had a direct positive effect on the behavioral intention to use smart homes. Additionally, intergenerational emotional and financial support affected life satisfaction, which subsequently influenced the behavioral intention to use smart homes. Discussion: The assistance and guidance provided by younger generations play a crucial role in shaping the willingness of older adults to adopt smart home technology. Intergenerational support can contribute positively to enabling aging individuals to age in place through the utilization of technology.

Whole-genome sequencing and transcriptome-characterized in vitro evolution of aminoglycoside resistance in Mycobacterium tuberculosis.

Antibiotic resistance of Mycobacterium tuberculosis (Mtb) is a major public health concern worldwide. Therefore, it is of great significance to characterize the mutational pathways by which susceptible Mtb evolves into drug resistance. In this study, we used laboratory evolution to explore the mutational pathways of aminoglycoside resistance. The level of resistance in amikacin inducing Mtb was also associated with changes in susceptibility to other anti-tuberculosis drugs such as isoniazid, levofloxacin and capreomycin. Whole-genome sequencing (WGS) revealed that the induced resistant Mtb strains had accumulated diverse mutations. We found that rrs A1401G was the predominant mutation in aminoglycoside-resistant clinical Mtb isolates from Guangdong. In addition, this study provided global insight into the characteristics of the transcriptome in four representative induced strains and revealed that rrs mutated and unmutated aminoglycoside-resistant Mtb strains have different transcriptional profiles. WGS analysis and transcriptional profiling of Mtb strains during evolution revealed that Mtb strains harbouring rrs A1401G have an evolutionary advantage over other drug-resistant strains under the pressure of aminoglycosides because of their ultra-high resistance level and low physiological impact on the strain. The results of this study should advance our understanding of aminoglycoside resistance mechanisms.

PKC-ζ mediated reduction of the extracellular vesicles-associated TGF-ß1 overcomes radiotherapy resistance in breast cancer.

BACKGROUND: Radiotherapy is widely applied in breast cancer treatment, while radiotherapy resistance is inevitable. TGF-ß1 has been considered to be an endogenous factor for the development of radiotherapy resistance. As a large portion of TGF-ß1 is secreted in an extracellular vesicles-associated form (TGF-ß1EV), particularly in radiated tumors. Thus, the understanding of the regulation mechanisms and the immunosuppressive functions of TGF-ß1EV will pave a way for overcoming the radiotherapy resistance in cancer treatment. METHODS: The superoxide-Zinc-PKC-ζ-TGF-ß1EV pathway in breast cancer cells was identified through sequence alignments of different PKC isoforms, speculation and experimental confirmation. A series of functional and molecular studies were performed by quantitative real-time PCR, western blot and flow cytometry analysis. Mice survival and tumor growth were recorded. Student's t test or two-way ANOVA with correction was used for comparisons of groups. RESULTS: The radiotherapy resulted in an increased expression of the intratumoral TGF-ß1 and an enhanced infiltration of the Tregs in the breast cancer tissues. The intratumoral TGF-ß1 was found mainly in the extracellular vesicles associated form both in the murine breast cancer model and in the human lung cancer tissues. Furthermore, radiation induced more TGF-ß1EV secretion and higher percentage of Tregs by promoting the expression and phosphorylation of protein kinase C zeta (PKC-ζ). Importantly, we found that naringenin rather than 1D11 significantly improved radiotherapy efficacy with less side effects. Distinct from TGF-ß1 neutralizing antibody 1D11, the mechanism of naringenin was to downregulate the radiation-activated superoxide-Zinc-PKC-ζ-TGF-ß1EV pathway. CONCLUSIONS: The superoxide-zinc-PKC-ζ-TGF-ß1EV release pathway was elucidated to induce the accumulation of Tregs, resulting in radiotherapy resistance in the TME. Therefore, targeting PKC-ζ to counteract TGF-ß1EV function could represent a novel strategy to overcome radiotherapy resistance in the treatment of breast cancer or other cancers. TRIAL REGISTRATION: The using of patient tissues with malignant Non-Small Cell Lung Cancer (NSCLC) was approved by the ethics committees at Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (NCC2022C-702, from June 8th, 2022).

The relationship between depressive symptoms and cognitive function in Alzheimer's disease: The mediating effect of amygdala functional connectivity and radiomic features.

BACKGROUND: Depressive symptoms are common in Alzheimer's disease (AD) and are associated with cognitive function. Amygdala functional connectivity (FC) and radiomic features related to depression and cognition. However, studies have yet to explore the neural mechanisms underlying these associations. METHODS: We enrolled eighty-two AD patients with depressive symptoms (ADD) and 85 healthy controls (HCs) in this study. We compared amygdala FC using the seed-based approach between ADD patients and HCs. The least absolute shrinkage and selection operator (LASSO) was used to select amygdala radiomic features. A support vector machine (SVM) model was constructed based on the identified radiomic features to distinguish ADD from HCs. We used mediation analyses to explore the mediating effects of amygdala radiomic features and amygdala FC on cognition. RESULTS: We found that ADD patients showed decreased amygdala FC with posterior cingulate cortex, middle frontal gyrus (MFG), and parahippocampal gyrus involved in the default mode network compared to HCs. The area under the receiver operating characteristic curve (AUC) of the amygdala radiomic model was 0.95 for ADD patients and HCs. Notably, the mediation model demonstrated that amygdala FC with the MFG and amygdala-based radiomic features mediated the relationship between depressive symptoms and cognitive function in AD. LIMITATIONS: This study is a cross-sectional study and lacks longitudinal data. CONCLUSION: Our findings may not only expand existing biological knowledge of the relationship between cognition and depressive symptoms in AD from the perspective of brain function and structure but also may ultimately provide potential targets for personalized treatment strategies.

The impact of perceived value and affection on Chinese residents' continuous use intention of mobile health science information: An empirical study.

Introduction: Disseminating health science information via the internet has become an essential means for improving Chinese residents' health literacy, which has received constant attention from the Chinese government. Therefore, it is important to explore Chinese residents' perceived value and emotional response to mobile health science information for determining Chinese residents' satisfaction and use intention. Methods: This study applied the cognition-affect-conation model to evaluate the perceived value, arousal, pleasure, trust, satisfaction, and continuous use intention. A mobile device was used to obtain health science information from 236 Chinese residents via an online survey and the data were analyzed using partial least squares (PLS)-structural equation modeling. Results: The results showed that Chinese residents' perceived value of health science information obtained using the mobile device directly affect the degree of arousal (ß = 0.412, P < 0.001), pleasure (ß = 0.215, P < 0.01), and trust (ß = 0.339, P < 0.001). The degree of arousal (ß = 0.121, P < 0.01), pleasure (ß = 0.188, P < 0.01), and trust (ß = 0.619, P < 0.001) directly affected Chinese residents' satisfaction, which further affected their continuous use intention (ß = 0.513, P < 0.001). Similarly, trust directly affected Chinese residents' continuous use intention (ß = 0.323, P < 0.001). The degree of arousal directly affected their degree of pleasure (ß = 0.304, P < 0.001), and pleasure also imposed a direct effect on trust (ß = 0.293, P < 0.001). Discussion: The result of this study provided an academic and practical reference to improve mobile health science popularization information. Affective changes have imposed an important effect on Chinese residents' continuous use intention. High-quality, diversified and frequent use of health science information can significantly increase residents' continuous use intention, improving their health literacy as a consequence.

The effect of hippocampal radiomic features and functional connectivity on the relationship between hippocampal volume and cognitive function in Alzheimer's disease.

Hippocampal volume is associated with cognitive function in Alzheimer's disease (AD). Hippocampal radiomic features and resting-state functional connectivity (rs-FC) are promising biomarkers and correlate with AD pathology. However, few studies have been conducted on how hippocampal biomarkers affect the cognition-structure relationship. Therefore, we aimed to investigate the effects of hippocampal radiomic features and resting-state functional connectivity (rs-FC) on this relationship in AD. We enrolled 70 AD patients and 65 healthy controls (HCs). The FreeSurfer software was used to measure hippocampal volume. We selected hippocampal radiomic features to build a model to distinguish AD patients from HCs and used a seed-based approach to calculate the hippocampal rs-FC. Furthermore, we conducted mediation and moderation analyses to investigate the effect of hippocampal radiomic features and rs-FC on the relationship between hippocampal volume and cognition in AD. The results suggested that hippocampal radiomic features mediated the association between bilateral hippocampal volume and cognition in AD. Additionally, patients with AD showed weaker rs-FC between the bilateral hippocampus and right ventral posterior cingulate cortex and stronger rs-FC between the left hippocampus and left insula than HCs. The rs-FC between the hippocampus and insula moderated the relationship between hippocampal volume and cognition in AD, suggesting that this rs-FC could exacerbate or ameliorate the effects of hippocampal volume on cognition and may be essential in improving cognitive function in AD. Our findings may not only expand existing biological knowledge of the interrelationships among hippocampal biomarkers and cognition but also provide potential targets for treatment strategies for AD.

Evaluation of Dalbavancin Use on Clinical Outcomes, Cost-Savings, and Adherence at a Large Safety Net Hospital.

Dalbavancin is a second-generation lipoglycopeptide antibiotic with activity against Gram-positive organisms. Dalbavancin is Food and Drug Administration (FDA)-approved for acute bacterial skin and soft tissue infections (ABSSTIs). There is a lack of substantial data on dalbavancin in more invasive infections, particularly in high-risk populations (patients with intravenous drug use and unstable living conditions). In this retrospective observational study, we reviewed all patients that received at least one dose of dalbavancin in an inpatient or outpatient setting at Parkland Hospital from February of 2019 to August of 2021. The demographics, type of infection, and rationale for dalbavancin were collected at the baseline. Clinical failure was measured by an avoidance of emergency department (ED) visits or hospital readmission at 30, 60, and 90 days. A separate analysis was conducted to estimate hospital, rehabilitation, or nursing facility days saved based on the projected length of treatment. 40 patients were included, and the majority were uninsured (85%), experiencing homelessness (60%), or had intravenous drug use (IDU) (57.5%). Indications for use included ABSSTIs (45%), bloodstream infection (67.5%), osteomyelitis (40%), infective endocarditis (10%), and septic arthritis (10%). Clinical failure was observed in 5 of the 40 patients (12.5%). Nonadherence to medical recommendations, a lack of source control, and ongoing IDU increased the risk of failure. Dalbavancin saved a total of 566 days of inpatient, rehabilitation, and nursing facility stays. Dalbavancin is a reasonable alternative to the standard of care in an at-risk population, offering decreased lengths of stays and cost savings. The uses of second-generation lipoglycopeptides are desirable alternatives to traditional outpatient parenteral antibiotic therapies for patients who otherwise would not qualify or for patients who desire less hospital contact in light of the COVID-19 pandemic. IMPORTANCE This study contributes additional experience to the literature of dalbavancin use in off-label indications, particularly for patients who do not qualify for outpatient parenteral antimicrobial therapy. The majority of the patient population were people who inject drugs and the uninsured. There is difficulty in tracking outcomes in this patient population, given their outpatient follow-up rates; however, we were able to track emergency room visits and readmissions throughout the majority of the local metroplex. The clinical use of dalbavancin at our institution also increased in the midst of the COVID-19 pandemic in an effort to preserve hospital resources and limit health care exposure. In addition, we are able to provide institution-specific cost-saving data with the use of dalbavancin.