Burden of neck pain in general population of China, 1990-2019: An analysis for the Global Burden of Disease Study 2019.

Background: Neck pain has become very common in China and has greatly affected individuals, families, and society in general. In this study, we aimed to report on the rates and trends of the prevalence, incidence, and years lived with disability (YLDs) caused by neck pain in the general population of China from 1990 to 2019. Methods: We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) study to estimate the number and age standardised rates per 100 000 population of neck pain point prevalence, annual incidence, and YLDs in 33 provinces/municipalities/autonomous regions of China, stratified by age, sex, and sociodemographic index (SDI) from 1990 to 2019. We then compared these estimates with other G20 countries. Results: There were 6.80 × 107 patients with neck pain in 2019, presenting an increase from 3.79 × 107 in 1990. Likewise, the national age-standardised point prevalence increased slightly from 3.53% in 1990 to 3.57% in 2019. The YLDs increased by 78.08%, from 3814 × 103 in 1990 to 6792 × 103 in 2019. The age-standardised YLDs rate increased 1.50% from 352.84 in 1990 to 358.10 in 2019. The point prevalence of neck pain in 2019 was higher in females compared with males. These estimates were all above the global average level and increased more rapidly among G20 countries from 1990 to 2019. We generally observed a positive association between age-standardised YLD rates for neck pain and SDI, suggesting the burden is higher at higher sociodemographic indices. Conclusions: Neck pain is a serious public health problem in the general population in China, especially in its central and western regions, with an overall increasing trend in the last three decades. This is possibly related to changes of people's lifestyles and work patterns due to improvements in societal well-being and technology. Raising awareness of risk factors for neck pain in the general population and establishing effective preventive and treatment strategies could help reduce the future burden of neck disorders.

A case of neonatal tsutsugamushi disease diagnosed with the aid of rickettsial macrogenomic detection.

BACKGROUND: Tsutsugamushi, also known as bush typhus, is a naturally occurring disease caused by Orientia tsutsugamushi. We reported a case of vertical mother-to-newborn transmission of Orientia tsutsugamushi infection in a newborn from Yunnan (China). CASE PRESENTATION: Decreased fetal movements were observed at 39 weeks of gestation. After birth, the newborn (female) had recurrent fever, shortness of breath, and bruising around the mouth and extremities. At 5 h 58 min of age, the newborn was admitted for fever, shortness of breath and generalized rash. The liver was palpable 3 cm below the costal margin, and the limbs showed pitting edema. There was subcutaneous bleeding. Investigations suggested heavy infection, myocardial damage, decreased platelets. Treatment with cefotaxime and ampicillin failed. The mother was hospitalized at 29 weeks of gestation with a fever for 4 consecutive days, and an ulcerated crust was found in the popliteal fossa. Due to this pregnancy history, A diagnosis of Orientia tsutsugamushi infection was suspected in our index case and confirmed by macrogenomic testing and she was treated with vancomycin and meropenem, and later azithromycin for 1 week. The newborn was discharged in good general condition, gradually normalizing body temperature, and decreasing rash and jaundice. There were no abnormalities on subsequent blood macrogenomic tests for the baby. And one month later she showed good mental health, sleep, and food intake and no fever, rash, or jaundice. CONCLUSION: Determining the cause of symptoms is the key to treating diseases, especially the rare diseases that can be misdiagnosed. SUITABLE FOR PEOPLE WITH: Infectious Diseases; Neonatology; Obstetrics.

Genetic landscape of breast cancer subtypes following radiation therapy: insights from comprehensive profiling.

Background: In breast cancer, in the era of precision cancer therapy, different patterns of genetic mutations dictate different treatments options. However, it is not clear whether the genetic profiling of breast cancer patients undergoing breast-conserving surgery is related to the adverse reactions caused by radiotherapy. Methods: We collected formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 54 breast cancer patients treated with radiation after breast-conserving surgery and identified comprehensive molecular information in hundreds of cancer-associated genes by FoundationOne CDx (F1CDx), a next-generation sequencing (NGS)-based assay. Results: Among our cohort of 54 breast cancer patients, we found high-frequency mutations in cancer-related genes such as TP53 (56%), RAD21 (39%), PIK3CA (35%), ERBB2 (24%), and MYC (22%). Strikingly, we detected that the WNT pathway appears to be a signaling pathway with specific high-frequency mutations in the HER2 subtype. We also compared the mutation frequencies of the two groups of patients with and without cutaneous radiation injury (CRI) after radiotherapy and found that the mutation frequencies of two genes, FGFR1 and KLHL6, were significantly higher in patients with CRI : No subgroup than in those with CRI : Yes. Conclusion: Different breast cancer subtypes have their own type-specific mutation patterns. FGFR1 and KLHL6 mutations are protective factors for radiation-induced skin toxicity in breast cancer patients.

DDX27 regulates oral squamous cell carcinoma development through targeting CSE1L.

THE HEADINGS AIMS: DEAD-box helicase 27 (DDX27), a member of the DEAD-Box nucleic acid helicase family, holds an elusive role in oral squamous cell carcinoma (OSCC). This study aims to unravel the regulatory functions of DDX27 in OSCC and explore its downstream targets. MATERIALS AND METHODS: A commercial oral squamous cell carcinoma (OSCC) tissue microarray (TMA) was utilized. We analyzed differentially expressed genes in OSCC through the GEO database. Target gene silencing was achieved using the shRNA-mediated lentivirus method. Coexpedia analysis identified co-expressed genes associated with DDX27. Additionally, a Co-Immunoprecipitation (Co-IP) experiment confirmed the protein interaction between DDX27 and CSE1L. Xenograft tumor models were employed to evaluate DDX27's role in OSCC tumor formation. KEY FINDINGS: Elevated DDX27 expression in OSCC correlated with a higher pathological grade. DDX27 knockdown resulted in decreased cell proliferation, increased apoptosis, inhibited cell migration, and induced G2/M phase cell cycle arrest, as well as impaired tumor outgrowth. Coexpedia analysis identified STAU1, NELFCD, and CSE1L as top co-expressed genes. Lentiviral vectors targeting STAU1, NELFCD, and CSE1L revealed that silencing CSE1L significantly impaired cell growth, indicating it as a downstream target of DDX27. Cell rescue experiments demonstrated that increased DDX27 levels ameliorated cell proliferation, attenuated apoptosis, and CSE1L depletion blocked cell development induced by DDX27 overexpression. SIGNIFICANCES: This study highlighted DDX27 as a potential therapeutic target for OSCC treatment, shedding light on its crucial role in OSCC development. Targeting DDX27 or its downstream effector, CSE1L, holds promise for innovative OSCC therapies.

Metformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortex.

Cognitive impairment is a core feature of schizophrenia, which is aggravated by antipsychotics-induced metabolic disturbance and lacks effective pharmacologic treatments in clinical practice. Our previous study demonstrated the efficiency of metformin in alleviating metabolic disturbance following antipsychotic administration. Here we report that metformin could ameliorate cognitive impairment and improve functional connectivity (FC) in prefrontal regions. This is an open-labeled, evaluator-blinded study. Clinically stable patients with schizophrenia were randomly assigned to receive antipsychotics plus metformin (N = 48) or antipsychotics alone (N = 24) for 24 weeks. The improvement in cognition was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Its association with metabolic measurements, and voxel-wise whole-brain FC with dorsolateral prefrontal cortex (DLPFC) subregions as seeds were evaluated. When compared to the antipsychotics alone group, the addition of metformin resulted in significantly greater improvements in the MCCB composite score, speed of processing, working memory, verbal learning, and visual learning. A significant time × group interaction effect of increased FC between DLPFC and the anterior cingulate cortex (ACC)/middle cingulate cortex (MCC), and between DLPFC subregions were observed after metformin treatment, which was positively correlated with MCCB cognitive performance. Furthermore, the FC between left DLPFC A9/46d to right ACC/MCC significantly mediated metformin-induced speed of processing improvement; the FC between left A46 to right ACC significantly mediated metformin-induced verbal learning improvement. Collectively, these findings demonstrate that metformin can improve cognitive impairments in schizophrenia patients and is partly related to the FC changes in the DLPFC. Trial Registration: The trial was registered with ClinicalTrials.gov (NCT03271866). The full trial protocol is provided in Supplementary Material.

BzATP reverses ferroptosis-induced gut microbiota disorders in collagen-induced arthritis mice.

Recent studies suggested that altered gut microbiota may be related to the pathogenesis of rheumatoid arthritis (RA), albeit the exact mechanisms are unknown. In this study, we aimed to discover the particular mechanism of RA treatment by microbiota by investigating the effects of ferroptosis on gut microbiota and its metabolites in collagen-induced arthritis (CIA) mice. Mice were divided into five groups: control, CIA, erastin, BzATP, and BzATP + erastin group. We performed 16S rDNA sequencing and metabolomics analysis on mouse feces and found that erastin and BzATP altered the microbiota and metabolites. The findings demonstrated that the microbiota was significantly disturbed at the phylum (Proteobacteria, Firmicutes, and Bacteroidota) and genus level (Lachnospiraceae_NK4A136, Lactobacillus, and Bifidobacterium) in the CIA group, and erastin exacerbated this disturbance. Unexpectedly, BzATP treatment could repair the disruptive effects of erastin. Additionally, there were significant variations in metabolites between each group. Erastin worsened metabolite abnormalities in CIA mice, while BzATP mitigated them, consistent with the microbiota results. These findings provide novel perspectives and insights into the therapy of RA.

Inhibition of tumor intrinsic BANF1 activates antitumor immune responses via cGAS-STING and enhances the efficacy of PD-1 blockade.

BACKGROUND: BANF1 is well known as a natural opponent of cyclic GMP-AMP synthase (cGAS) activity on genomic self-DNA. However, the roles of BANF1 in tumor immunity remain unclear. Here, we investigate the possible impact of BANF1 on antitumor immunity and response to immunotherapy. METHODS: The Cancer Genome Atlas public data were analyzed to evaluate the relevance of the expression of BANF1, patients' survival and immune cell infiltration. We monitored tumor growth and explored the antitumor efficacy of targeting tumor-intrinsic BANF1 in combination with anti-programmed cell death protein-1 (PD-1) in MC38 or B16F10 tumor models in both immunocompetent and immunodeficient mice. Flow cytometry, immunofluorescence and T cells depletion experiments were used to validate the role of BANF1 in tumor immune microenvironment reprogramming. RNA sequencing was then used to interrogate the mechanisms how BANF1 regulated antitumor immunity. RESULTS: We show that upregulated expression of BANF1 in tumor tissues is significantly associated with poor survival and is negatively correlated with immune cell infiltration. Deficiency of BANF1 in tumor cells markedly antagonizes tumor growth in immunocompetent but not immunocompromised mice, and enhances the response to immunotherapy in murine models of melanoma and colon cancer. In the immunotherapy clinical cohort, patients with high BANF1 expression had a worse prognosis. Mechanistically, BANF1 knockout activates antitumor immune responses mediated by cGAS-synthase-stimulator of interferon genes (cGAS-STING) pathway, resulting in an immune-activating tumor microenvironment including increased CD8+ T cell infiltration and decreased myeloid-derived suppressor cell enrichment. CONCLUSIONS: BANF1 is a key regulator of antitumor immunity mediated by cGAS-STING pathway. Therefore, our study provides a rational that targeting BANF1 is a potent strategy for enhancing immunotherapy for cancer with BANF1 upregulation.

Metagenomics reveals the abundance and accumulation trend of antibiotic resistance gene profile under long-term no tillage in a rainfed agroecosystem.

Widespread soil resistance can seriously endanger sustainable food production and soil health. Conservation tillage is a promising practice for improving soil structure and health. However, the impact of long-term no-tillage on the presence of antibiotic resistance genes in agricultural soils remains unexplored. Based on the long-term (>11 yr) tillage experimental fields that include both conservation tillage practices [no tillage (ZT)] and conventional tillage practices [plough tillage (PT)], we investigated the accumulation trend of antibiotic resistance genes (ARGs) in farmland soils under long-term no-tillage conditions. We aimed to provide a scientific basis for formulating agricultural production strategies to promote ecological environment safety and human health. In comparison to PT, ZT led to a considerable reduction in the relative abundance of both antibiotic resistance genes and antibiotic target gene families in the soil. Furthermore, the abundance of all ARGs were considerably lower in the ZT soil. The classification of drug resistance showed that ZT substantially decreased the relative abundance of Ethambutol (59.97%), ß-lactams (44.87%), Fosfomycin (35.82%), Sulfonamides (34.64%), Polymyxins (33.67%), MLSB (32.78%), Chloramphenicol (28.57%), Multi-drug resistance (26.22%), Efflux pump (23.46%), Aminoglycosides (16.79%), Trimethoprim (13.21%), Isoniazid (11.34%), Fluoroquinolone (6.21%) resistance genes, compared to PT soil. In addition, the abundance of the bacterial phyla Proteobacteria, Actinobacteria, Acidobacteria, and Gemmatimonadetes decreased considerably. The Mantel test indicated that long-term ZT practices substantially increased the abundance of beneficial microbial flora and inhibited the enrichment of ARGs in soil by improving soil microbial diversity, metabolic activity, increasing SOC, TN, and available Zn, and decreasing pH. Overall, long-term no-tillage practices inhibit the accumulation of antibiotic resistance genes in farmland soil, which is a promising agricultural management measure to reduce the accumulation risk of soil ARGs.

Long noncoding RNA signatures in intrauterine infection/inflammation-induced lung injury: an integrative bioinformatics study.

BACKGROUND: Intrauterine infection/inflammation can result in fetal and neonatal lung injury. However, the biological mechanisms of intrauterine infection/inflammation on fetal and neonatal lung injury and development are poorly known. To date, there are no reliable biomarkers for improving intrauterine infection/inflammation-induced lung injury. METHODS: An animal model of intrauterine infection/inflammation-induced lung injury was established with pregnant Sprague-Dawley rats inoculated with Escherichia coli suspension. The intrauterine inflammatory status was assessed through the histological examination of the placenta and uterus. A serial of histological examinations of the fetal and neonatal rats lung tissues were performed. The fetal and neonatal rat lung tissues were harvested for next generation sequencing at embryonic day 17 and postnatal day 3, respectively. Differentially expressed mRNAs and lncRNAs were identified by conducting high-throughput sequencing technique. The target genes of identified differentially expressed lncRNAs were analyzed. Homology analyses for important differentially expressed lncRNAs were performed. RESULTS: The histopathological results showed inflammatory infiltration, impaired alveolar vesicular structure, less alveolar numbers, and thickened alveolar septa in fetal and neonatal rat lung tissues. Transmission electron micrographs revealed inflammatory cellular swelling associated with diffuse alveolar damage and less surfactant-storing lamellar bodies in alveolar epithelial type II cells. As compared with the control group, there were 432 differentially expressed lncRNAs at embryonic day 17 and 125 differentially expressed lncRNAs at postnatal day 3 in the intrauterine infection group. The distribution, expression level, and function of these lncRNAs were shown in the rat genome. LncRNA TCONS_00009865, lncRNA TCONS_00030049, lncRNA TCONS_00081686, lncRNA TCONS_00091647, lncRNA TCONS_00175309, lncRNA TCONS_00255085, lncRNA TCONS_00277162, and lncRNA TCONS_00157962 may play an important role in intrauterine infection/inflammation-induced lung injury. Fifty homologous sequences in Homo sapiens were also identified. CONCLUSIONS: This study provides genome-wide identification of novel lncRNAs which may serve as potential diagnostic biomarkers and therapeutic targets for intrauterine infection/inflammation-induced lung injury.

Autophagy in the pharmacological activities of celastrol (Review).

Celastrol, a natural compound extracted from the traditional Chinese medicinal herb Tripterygium wilfordii Hook F, possesses broad-spectrum pharmacological properties. Autophagy is an evolutionarily conserved catabolic process through which cytoplasmic cargo is delivered to the lysosomes for degradation. Autophagy dysregulation contributes to multiple pathological processes. Therefore, targeting autophagic activity is a promising therapy for various diseases, as well as a drug-development strategy. According to previous studies, autophagy is specifically targeted and may be altered in response to celastrol treatment, highlighting that autophagy modulation is an important mechanism underlying the therapeutic efficacy of celastrol for the treatment of various diseases. The present study summarizes the currently available information regarding the role of autophagy in the effect of celastrol to exert anti-tumor, anti-inflammatory, immunomodulatory, neuroprotective, anti-atherosclerosis, anti-pulmonary fibrosis and anti-macular degeneration activities. The diverse signaling pathways involved are also analyzed to provide insight into the mechanisms of action of celastrol and thereby pave the way for establishing celastrol as an efficacious autophagy modulator in clinical practice.

Disrupted functional connectivity of the cerebellum with default mode and frontoparietal networks in young adults with major depressive disorder.

Cerebellar dysconnectivity has repeatedly been documented in major depressive disorder (MDD). The cerebellum is composed of multiple functionally distinct subunits, and whether those subunits show similar or distinct dysconnectivity patterns with the cerebrum in MDD, is still unclear and needs to be further clarified. In this study, 91 MDD patients (23 male and 68 female) and 59 demographically matched healthy controls (22 male and 37 female) were enrolled to explore the cerebellar-cerebral dysconnectivity pattern in MDD by using the cutting-edge cerebellar partition atlas. Results showed that MDD patients exhibit decreased cerebellar connectivity with cerebral regions of default mode (DMN), frontoparietal networks (FPN), and visual areas. The dysconnectivity pattern was statistically similar across cerebellar subunits, with no significant diagnosis-by-subunit interactions. Correlation analyzes showed that cerebellar-dorsal lateral prefrontal cortex (DLPFC) connectivity is significantly correlated with anhedonia in MDD patients. Such dysconnectivity pattern was not affected by sex, which, however, should be further replicated in larger samples. These findings suggest a generalized disrupted cerebellar-cerebral connectivity pattern in MDD across all cerebellar subunits, which partially accounts for depressive symptoms in MDD, thus highlighting the pivotal role of the disrupted connectivity of cerebellum with DMN and FPN in the neuropathology of depression.

Exopolysaccharide-producing bacteria enhanced Pb immobilization and influenced the microbiome composition in rhizosphere soil of pakchoi (Brassica chinensis L.).

Lead (Pb) contamination of planting soils is increasingly serious, leading to harmful effects on soil microflora and food safety. Exopolysaccharides (EPSs) are carbohydrate polymers produced and secreted by microorganisms, which are efficient biosorbent materials and has been widely used in wastewater treatment to remove heavy metals. However, the effects and underlying mechanism of EPS-producing marine bacteria on soil metal immobilization, plant growth and health remain unclear. The potential of Pseudoalteromonas agarivorans Hao 2018, a high EPS-producing marine bacterium, to produce EPS in soil filtrate, immobilize Pb, and inhibit its uptake by pakchoi (Brassica chinensis L.) was studied in this work. The effects of strain Hao 2018 on the biomass, quality, and rhizospheric soil bacterial community of pakchoi in Pb-contaminated soil were further investigated. The results showed that Hao 2018 reduced the Pb concentration in soil filtrate (16%-75%), and its EPS production increased in the presence of Pb2+. When compared to the control, Hao 2018 remarkably enhanced pakchoi biomass (10.3%-14.3%), decreased Pb content in edible tissues (14.5%-39.2%) and roots (41.3%-41.9%), and reduced the available Pb content (34.8%-38.1%) in the Pb-contaminated soil. Inoculation with Hao 2018 raised the pH of the soil, the activity of several enzymes (alkaline phosphatase, urease, and dehydrogenase), the nitrogen content (NH4 +-N and NO3 --N), and the pakchoi quality (Vc and soluble protein content), while also raising the relative abundance of bacteria that promote plant growth and immobilize metals, such as Streptomyces and Sphingomonas. In conclusion, Hao 2018 reduced the available Pb in soil and pakchoi Pb absorption by increasing the pH and activity of multiple enzymes and regulating microbiome composition in rhizospheric soil.

Relapse in patients with schizophrenia and amisulpride-induced hyperprolactinemia or olanzapine-induced metabolic disturbance after switching to other antipsychotics.

Hyperprolactinemia and metabolic disturbance are common side effects of antipsychotics that cause intolerance. Despite its potential influence on relapse, there are no established guidelines for antipsychotic switching. This naturalistic study explored the association between antipsychotic switching, baseline clinical status, metabolic changes, and relapse in patients with schizophrenia. In total, 177 patients with amisulpride-induced hyperprolactinemia and 274 with olanzapine-induced metabolic disturbance were enrolled. Relapse was determined by assessing changes in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to 6 months (increased over 20% or 10% reaching 70). Metabolic indices were measured at baseline and 3 months. Patients with baseline PANSS >60 were more likely to relapse. Further, patients switching to aripiprazole had a higher risk of relapse regardless of their original medication. Participants who originally used amisulpride had reduced prolactin levels following medication change, while switching to olanzapine caused increased weight and blood glucose levels. In patients originally using olanzapine, only switching to aripiprazole reduced insulin resistance. Adverse effects on weight and lipid metabolism were observed in patients who switched to risperidone, while amisulpride improved lipid profiles. Changing schizophrenia treatment requires careful consideration of multiple variables, particularly the choice of substituted drug and the patient's baseline symptoms.

Validation, analysis, and comparison of MISR V23 aerosol optical depth products with MODIS and AERONET observations.

The latest Multi-angle Imaging Spectro Radiometer (MISR) Version (V) 23 aerosol optical depth (AOD) products were released, with an improved spatial resolution of 4.4 km, providing an unprecedented opportunity for the refined regional application. To ensure the reliability of their applications and build a scientific reference for the further optimization, it is imperative to conduct a comprehensive evaluation, especially for the unique size-resolved AOD products: small-size AOD (AODS, representing the contribution of fine-mode aerosols), medium-size AOD (AODM), and large-size AOD (AODL), and AODM+L represents the AOD part of coarse-mode aerosols. AErosol RObotic NETwork (AERONET) and MODerate-resolution Imaging Spectroradiometer (MODIS) Collection (C) 6.1 aerosol products from 2001 to 2020 are utilized for the validation, analysis, and inter-comparison, considering three spatial scales and four key factors. In general, MISR V23 aerosol products show a good accuracy compared with AERONET. The best performance for all AOD products appears in forest units (the highest R ~ 0.93, data percentage within Expected Error bounds, %EE > 93), related to the inactive human activity and dark underlying surface. Dependences of retrieval deviations illustrate that the performance of MISR AOD deteriorates as aerosol loading increases. Namely, with the increase of aerosols, total AOD (AODT) and AODS show increasing negative deviations, while increasing positive deviations are observed for AODM+L. This suggests that the Empirical Orthogonal Functions do not perform well in this situation, since numerous aerosol particles can obstruct the underlying reflection and reduce the surface spectral contrast. In addition, AODT and AODS often exhibit anomalous positive deviations in areas with low vegetation cover, such as deserts, revealing that MISR will overestimate aerosol content over bright surfaces and in environments dominated by coarse-mode particles. The above findings not only deepen the understanding of MISR aerosols products from multiple perspectives, but also provide useful information for the product improvement.

Hydrogen sulfide protects retinal pigment epithelium cells against ferroptosis through the AMPK- and p62-dependent non-canonical NRF2-KEAP1 pathway.

Oxidative stress-induced ferroptosis of retinal pigment epithelium (RPE) cells contributes to retinal degenerative diseases. The antioxidant molecule hydrogen sulfide (H2S) regulates oxidative stress response, but its effect on the ferroptosis of RPE cells is unclear. In this study, sodium hydrosulfide (NaHS) was used as an exogenous H2S donor to intervene tert-butyl hydroperoxide (t-BHP)-induced ferroptosis of APRE-19 cells. We found that NaHS pretreatment attenuates t-BHP-induced oxidative stress and ferroptosis. Analysis of mRNA-sequencing coupled with FerrDb database identified nuclear factor erythroid-2-related factor 2 (NRF2) as a primary target for the cytoprotective role of H2S. NRF2 inhibitor ML385 reverses the effects of H2S on ferroptosis. Biochemical analysis revealed that H2S stabilizes NRF2. H2S decreases the interaction between NRF2 and KEAP1, but enhances the interaction between KEAP1 and p62. These results suggest that H2S activates the non-canonical NRF2-KEAP1 pathway. Further study demonstrated that H2S stimulates AMPK to interact and phosphorylate p62. Additionally, inhibiting AMPK or knocking down p62 blocks the effects of H2S. We speculate that targeting the non-canonical NRF2-KEAP1 pathway by H2S-based drug may benefit the treatment of retinal degenerative diseases.

Inhibitory Effects of Myriocin on Non-Enzymatic Glycation of Bovine Serum Albumin.

Advanced glycation end products (AGEs) are the compounds produced by non-enzymatic glycation of proteins, which are involved in diabetic-related complications. To investigate the potential anti-glycation activity of Myriocin (Myr), a fungal metabolite of Cordyceps, the effect of Myr on the formation of AGEs resulted from the glycation of bovine serum albumin (BSA) and the interaction between Myr and BSA were studied by multiple spectroscopic techniques and computational simulations. We found that Myr inhibited the formation of AGEs at the end stage of glycation reaction and exhibited strong anti-fibrillation activity. Spectroscopic analysis revealed that Myr quenched the fluorescence of BSA in a static process, with the possible formation of a complex (approximate molar ratio of 1:1). The binding between BSA and Myr mainly depended on van der Waals interaction, hydrophobic interactions and hydrogen bond. The synchronous fluorescence and UV-visible (UV-vis) spectra results indicated that the conformation of BSA altered in the presence of Myr. The fluorescent probe displacement experiments and molecular docking suggested that Myr primarily bound to binding site 1 (subdomain IIA) of BSA. These findings demonstrate that Myr is a potential anti-glycation agent and provide a theoretical basis for the further functional research of Myr in the prevention and treatment of AGEs-related diseases.

Identifying and revealing different brain neural activities of cognitive subtypes in early course schizophrenia.

Background: Cognitive subtypes of schizophrenia may exhibit different neurobiological characteristics. This study aimed to reveal the underlying neurobiological features between cognitive subtypes in the early course of schizophrenia (ECS). According to prior studies, we hypothesized to identify 2-4 distinct cognitive subtypes. We further hypothesized that the subtype with relatively poorer cognitive function might have lower brain spontaneous neural activity than the subtype with relatively better cognitive function. Method: Cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Resting-state functional magnetic resonance imaging scanning was conducted for each individual. There were 155 ECS individuals and 97 healthy controls (HCs) included in the subsequent analysis. Latent profile analysis (LPA) was used to identify the cognitive subtypes in ECS individuals, and amplitude of low-frequency fluctuations (ALFFs) was used to measure brain spontaneous neural activity in ECS individuals and HCs. Results: LPA identified two cognitive subtypes in ECS individuals, containing a severely impaired subtype (SI, n = 63) and a moderately impaired subtype (MI, n = 92). Compared to HCs, ECS individuals exhibited significantly increased ALFF in the left caudate and bilateral thalamus and decreased ALFF in the bilateral medial prefrontal cortex and bilateral posterior cingulate cortex/precuneus (PCC/PCu). In ECS cognitive subtypes, SI showed significantly higher ALFF in the left precentral gyrus (PreCG) and lower ALFF in the left PCC/PCu than MI. Furthermore, ALFFs of left PreCG were negatively correlated with several MCCB cognitive domains in ECS individuals, while ALFF of left PCC/PCu presented opposite correlations. Conclusion: Our findings suggest that differences in the brain spontaneous neural activity of PreCG and PCC/PCu might be the potential neurobiological features of the cognitive subtypes in ECS, which may deepen our understanding of the role of PreCG and PCC/PCu in the pathogenesis of cognitive impairment in schizophrenia.

Controlling Phase Transition toward Future Low-Cost and Eco-friendly Printing of Perovskite Solar Cells.

Perovskite solar cells (PSCs) have grown increasingly popular over the past few years and are considered to be game-changers in the energy conversion market. It has became vital to transfer the deep understanding of the perovskite film formation process during lab-scale fabrication to large-scale production. Complex phase transition during film formation has been revealed by in situ strategies. However, there is still debate which phase transition is the right route for a future scalable approach. Herein, we briefly summarize perovskite crystallization during scalable printing processes. The critical information about the intermediates involved in phase transition from precursors to perovskite crystals are discussed because it deeply impacts the morphology of printed films. Finally, important strategies to control phase transition and challenges toward future low-temperature and eco-friendly printing of perovskite solar cells are proposed. The information provided by this Perspective will assist the screening and development of the perovskite phase transition for future cost-efficient printed perovskite panels.

Yb/Er/Ho-engineered rare earth fluoride nanoparticles to unlock multimodal in vivo medical imaging.

Fluorescence imaging with advanced multi-channel observation, high sensitivity, and high spatio-temporal resolution holds great promise for biomedical applications. However, the different absorption and scattering spectra of complex tissue structures present significant challenges for real-time investigations of live biological and physiological processes. Herein, we present Yb/Er/Ho-engineered rare earth fluoride nanoparticles with integrated multimodal imaging functions that can provide synergistic effects over any modality alone. The engineered nanoparticles can realize efficient and accurate diagnoses in clinical research. Employing Yb3+ sensitizers and both Er3+ and Ho3+ emitters, NaGdF4:15%Yb,15%Er,x%Ho nanoparticles absorb an excitation wavelength of 980 nm and emit luminescence centered at 1525 nm and 1155 nm in the second near-infrared (NIR-II) window. In addition, upconversion emission in the visible region is also observed for multiplex signals. T1- and T2-weighted magnetic resonance (MR) imaging is achieved owing to the presence of paramagnetic Gd3+ and Ho3+ species. The high X-ray attenuation ability of the elemental constituents permits the use of the prepared nanoparticles as high-contrast X-ray computed tomography (CT) imaging agents. Taken together, this study shows the construction of an alternative multimodal nanoprobe with synergistic T1- and T2-MR/CT/downconversion luminescence (DCL) imaging abilities, which can provide an alternative approach for in vivo disease diagnosis and supervision.

The effects of probiotics plus dietary fiber on antipsychotic-induced weight gain: a randomized clinical trial.

Probiotics plus dietary fiber has demonstrated efficacy in improving metabolic abnormalities. However, the efficacy of probiotics and dietary fiber as well as their association with microbiota in attenuating antipsychotic-induced weight gain and metabolic disturbance remains poorly understood. Here we analyzed results from the double-blind, randomized, placebo-controlled study to compare and evaluate the effects of probiotics, dietary fiber, and their combination for antipsychotic-induced weight gain in patients with a severe mental disorder. We found that probiotics plus dietary fiber was significantly superior to probiotics alone, dietary fiber only, and the placebo for weight, BMI, and total cholesterol reduction; insulin resistance was worse in the placebo group, with significant increases during the 12-week treatment; probiotics plus dietary fiber significantly reduced weight and prevented further deterioration of metabolic disturbances; and probiotics or dietary fiber alone can prevent further weight gain. We further performed 16 S ribosomal RNA sequencing revealed an increased abundance of microbiota after probiotics plus dietary fiber treatment. Moreover, logistic regression analyses revealed that the higher richness of microbiota was associated with favorable weight loss. These findings suggested that probiotics and dietary fiber co-administration were safe and effective interventions to reduce weight gain in patients treated with antipsychotic medications.