Luteolin Inhibits Lung Cancer Cell Migration by Negatively Regulating TWIST1 and MMP2 Through Upregulation of miR-106a-5p.

BACKGROUND: Luteolin, a common dietary flavonoid found in plants, has been shown to have anti-cancer properties. However, its exact mechanisms of action in non-small cell lung cancer (NSCLC) are still not fully understood, particularly its role in regulating broader genomic networks and specific gene targets. In this study, we aimed to elucidate the role of microRNAs (miRNAs) in NSCLC treated with luteolin, using A549 cells as a model system. MATERIALS AND METHODS: miRNA profiling was conducted on luteolin-treated A549 cells using Exiqon microarrays, with validation of selected miRNAs by qRT-PCR. Bioinformatic analysis identified the regulatory roles of miRNAs in biological processes and pathways following luteolin treatment. Computational algorithms were employed to identify potential target genes. A549 cells were transfected with miR-106a-5p mimic and inhibitor or their corresponding controls. The expression levels of 2 genes, twist basic helix-loop-helix transcription factor 1 (TWIST1) and matrix metallopeptidase 2 (MMP2), and cell migration were assessed. RESULTS: miRNA profiling identified 341 miRNAs, with 18 exhibiting significantly altered expression (P < 0.05). Subsequent qRT-PCR analysis confirmed altered expression of 6 selected miRNAs. KEGG and GO analyses revealed significant alterations in pathways and biological processes crucial for tumor biology. TWIST1 and MMP2, which both contain conserved miR-106a-5p binding sites, exhibited an inverse correlation with the expression levels of miR-106a-5p. Dual-luciferase reporter assays confirmed TWIST1 and MMP2 as direct targets of miR-106a-5p. Luteolin treatment led to a reduction in A549 cell migration, and this reduction was further amplified by the overexpression of miR-106a-5p. CONCLUSION: Luteolin inhibits A549 cell migration by modulating the miRNA landscape, shedding light on its mechanisms and laying the foundation for miRNA-based therapeutic approaches for NSCLC.

Rational and design of prophylactic cranial irradiation (PCI) and brain MRI surveillance versus brain MRI surveillance alone in patients with limited-stage small cell lung cancer achieving complete remission (CR) of tumor after chemoradiotherapy: a multicenter prospective randomized study.

BACKGROUND: Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged. METHODS: A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4-6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI surveillance arm, receiving PCI (2.5 Gy qd to a total dose of 25 Gy in two weeks) followed by brain MRI surveillance once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective is to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives include 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detect during follow-up, stereotactic radiosurgery (SRS) will be recommended if patients meet the eligibility criteria. DISCUSSION: Based on our post-hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI.

PKM2 interacts with and phosphorylates PHB2 to sustain mitochondrial quality control against septic cerebral-cardiac injury.

Sepsis induces profound disruptions in cellular homeostasis, particularly impacting mitochondrial function in cardiovascular and cerebrovascular systems. This study elucidates the regulatory role of the Pyruvate Kinase M2 (PKM2)- Prohibitin 2 (PHB2) axis in mitochondrial quality control during septic challenges and its protective effects against myocardial and cerebral injuries. Employing LPS-induced mouse models, we demonstrate a significant downregulation of PKM2 and PHB2 in both heart and brain tissues post-sepsis, with corresponding impairments in mitochondrial dynamics, including fission, fusion, and mitophagy. Overexpression of PKM2 and PHB2 not only restores mitochondrial function, as evidenced by normalized ATP production and membrane potential but also confers resistance to oxidative stress by mitigating reactive oxygen species generation. These cellular mechanisms translate into substantial in vivo benefits, with transgenic mice overexpressing PKM2 or PHB2 displaying remarkable resistance to sepsis-induced cardiomyocyte and neuronal apoptosis, and organ dysfunction. Our findings highlight the PKM2-PHB2 interaction as a novel therapeutic target for sepsis, providing a foundation for future research into mitochondrial-based interventions to treat this condition. The study's insights into the molecular underpinnings of sepsis-induced organ failure pave the way for potential clinical applications in the management of sepsis and related pathologies.

Vulnerability Analysis Method Based on Network and Copula Entropy.

With the deepening of the diversification and openness of financial systems, financial vulnerability, as an endogenous attribute of financial systems, becomes an important measurement of financial security. Based on a network analysis, we introduce a network curvature indicator improved by Copula entropy as an innovative metric of financial vulnerability. Compared with the previous network curvature analysis method, the CE-based curvature proposed in this paper can measure market vulnerability and systematic risk with significant advantages.

The impact of residential environment on older people's capabilities to live independently: a survey in Beijing.

BACKGROUND: Studies have shown how environmental factors influence older people's health and functional limitations, which are crucial for achieving healthy aging. However, such a healthy aging model has been criticized for defining health as an absence of disease, because chronic conditions cannot be reversed through medical treatments. In response to such critiques, this study refers to Huber's positive health definition, arguing that health should not be defined as the absence of disease but as the ability to adapt and self-manage in the face of social, physical, and emotional challenges. There is a need to develop a community-based approach to healthy aging that considers how the residential environment enables older people to adapt and self-manage. Drawing on Sen's capability approach, this study proposes that such a community-based approach should provide a supportive environment to enable older people's capabilities to live independently. METHODS: Using hierarchical multiple regression analysis of data from 650 older people (60 years and older) surveyed in Beijing, we unravel which features of the residential environment support older people' s capabilities to live independently and how these impacts differ depending on older people's frailty levels. RESULTS: The results show that four environmental factors, namely perceived accessibility (B = 0.238, p < 0.001 for physical capability, B = 0.126, p < 0.001 for social capability, B = 0.195, p < 0.001 for psychological capability), pleasant surroundings (B = 0.079, p < 0.05 for physical capability, B = 0.065, p < 0.05 for social capability), meeting opportunities (B = 0.256, p < 0.001 for social capability, B = 0.188, p < 0,001 for psychological capability, and life convenience B = 0.089, p < 0.05 for physical capability, B = 0.153, p < 0.001 for psychological capability) positively affect older people's capabilities to live independently. These four environmental factors cause differences in older people's capabilities between different neighborhood types. Moderation analysis shows that meeting opportunities are more relevant for frail older people (B = 0.090, p < 0.001 for social capability, B = 0.086, p < 0.01 for psychological capability). CONCLUSIONS: This study contributes to the literature by emphasizing the role of supportive residential environments in enabling older people to live independently. Furthermore, we identify four environmental factors that support older people's capabilities. Results can be used to develop effective community-based environmental support to enable older people to live independently.

Talaromyces marneffei endocarditis initially detected by Next Generation Sequencing: A case report.

BACKGROUND: Talaromyces marneffei (T. marneffei) is a thermal dimorphic fungus, which can cause lung or blood stream infection in patients, often life-threatening. However, endocarditis caused by T. marneffei has not been reported. For elderly patients with implanted cardiac devices or artificial valves, the prevention and treatment of infective endocarditis should not be ignored. METHODS: This is a descriptive study of a T. marneffei endocarditis by joint detection of cardiac ultrasound examination, peripheral blood DNA metagenomics Next Generation Sequencing (mNGS), and in vitro culture. RESULTS: We describe an 80-year-old female patient with an unusual infection of T. marneffei endocarditis. After intravenous drip of 0.2 g voriconazole twice a day for antifungal treatment, the patient showed no signs of improvement and their family refused further treatment. CONCLUSION: Infective endocarditis is becoming more and more common in the elderly due to the widely use of invasive surgical procedures and implantation of intracardiac devices. The diagnosis and treatment of T. marneffei endocarditis is challenging because of its rarity. Here, we discussed a case of T. marneffei endocarditis, and emphasized the role of mNGS in early diagnosis, which is of great significance for treatment and survival rate of patients.

Higher serum ascorbic acid levels are associated with lower depression prevalence in US adults: a case-control study.

Background: Recent studies have shown that a higher intake of ascorbic acid was associated with a lower prevalence of depression. Nevertheless, the recall bias was common in dietary surveys in these studies, and it was ignored that there were differences in the absorption and utilization of ascorbic acid in the body. Hence, we aim to investigate the association between serum ascorbic acid levels and the prevalence of depression in US adults. Methods: A total of 3,404 participants from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) that underwent measurement of the Patient Health Questionnaire-9 (PHQ-9) scores and serum levels of ascorbic acid. Propensity Score Matching (PSM) successfully established a case-control study, comprising 299 participants diagnosed with depression and 1,107 as controls. We used binary logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to explore associated risk factors for depression. Restricted cubic splines (RCS) were used to show the nonlinear relationship between serum ascorbic acid levels and the prevalence of depression. Results: The prevalence of depression was approximately 8.8%, with a median serum ascorbic acid level of 49.9 (36.0, 67.0) µmol/L. Results revealed that the serum ascorbic acid levels of depressed patients were significantly lower than those of non-depressed individuals (42.97 VS 52.97 µmol/L). The baseline data indicated that as serum ascorbic acid levels increased from Quartile 1 (Q1) to Quartile 4 (Q4), the depression prevalence decreased from 12.0 to 5.4% (p < 0.05). The results of the chi-square test after PSM showed that serum ascorbic acid was still statistically significant (p < 0.001) with the prevalence of depression. Forest plot showed that compared with the Q1 of serum ascorbic acid level, the OR and 95%CI of depression prevalence in Q4 was 0.42 (0.30 ~ 0.61), and the adjusted OR and 95%CI of depressive prevalence was 0.49 (0.33 ~ 0.73). RCS models showed an L-shaped nonlinear relationship (P for nonlinearity <0.05) between serum ascorbic acid and depression. Conclusion: Our results suggested that higher serum ascorbic acid levels are associated with a reduced prevalence of depression.

Neuroprotective Effects of CXCR2 Antagonist SB332235 on Traumatic Brain Injury Through Suppressing NLRP3 Inflammasome.

The inflammatory process mediated by nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain comprising 3 (NLRP3) inflammasome plays a predominant role in the neurological dysfunction following traumatic brain injury (TBI). SB332235, a highly selective antagonist of chemokine receptor 2 (CXCR2), has been demonstrated to exhibit anti-inflammatory properties and improve neurological outcomes in the central nervous system. We aimed to determine the neuroprotective effects of SB332235 in the acute phase after TBI in mice and to elucidate its underlying mechanisms. Male C57BL/6J animals were exposed to a controlled cortical impact, then received 4 doses of SB332235, with the first dose administered at 30 min after TBI, followed by additional doses at 6, 24, and 30 h. Neurological defects were assessed by the modified neurological severity score, while the motor function was evaluated using the beam balance and open field tests. Cognitive performance was evaluated using the novel object recognition test. Brain tissues were collected for pathological, Western blot, and immunohistochemical analyses. The results showed that SB332235 significantly ameliorated TBI-induced deficits, including motor and cognitive impairments. SB332235 administration suppressed expression of both CXCL1 and CXCR2 in TBI. Moreover, SB332235 substantially mitigated the augmented expression levels and activation of the NLRP3 inflammasome within the peri-contusional cortex induced by TBI. This was accompanied by the blocking of subsequent production of pro-inflammatory cytokines. Additionally, SB332235 hindered microglial activity induced by TBI. These findings confirmed the neuroprotective effects of SB332235 against TBI, and the involved mechanisms were in part due to the suppression of NLRP3 inflammasome activity. This study suggests that SB332235 may act as an anti-inflammatory agent to improve functional outcomes in brain injury when applied clinically.

Metagenomic next-generation sequencing testing from the perspective of clinical benefits.

BACKGROUND AND AIMS: Metagenomic next-generation sequencing (mNGS) provided promising supports to rapid pathogen diagnosis. However, summary of scientific application strategy based on clinical practice study is still necessary for enhancing clinical benefits. MATERIALS AND METHODS: We conducted a retrospective analysis of 775 samples from patients with suspected infectious diseases (IDs). Based on final diagnosis, diagnostic performance, clinical relevance and clinical impact of mNGS among various clinical settings were assessed, and influencing factors were deeply explored. RESULTS: 84.26 % tests were clinically relevant; sample, but not sequencing, was the influencing factor. 40.77 % tests contributed to positive clinical impact, while 0.13 % and 59.10 % to negative and no impact respectively. mNGS utility in patients with IDs, definite infection site, BALF and CSF contributed to higher positive impacts. Days of empirical treatment before sampling ≤ 5 in ICU and ≤ 2 or between 11 and 20 in non-ICU, and reporting in 2 days brought about higher clinical benefit rates. Characteristic pathogen spectrum between ICU and non-ICU cases were revealed. CONCLUSIONS: Our findings highlighted clinical benefits from mNGS varied among different clinical settings, and elucidated choices on patients, samples, sampling and reporting time were four key factors. Rational strategy should be concerned to promote scientific application of mNGS and better improve clinical value.

Gardenia Iridoid Glucosides Protect Against α-Naphthalene Isothiocya-Nate-Induced Cholestatic Rats Through Activation of the FXR-SHP Signaling Pathway.

Introduction: Cholestasis is a common liver disorder that currently has limited treatment options. Gardenia Iridoid Glucosides (GIG) have been found to possess various physiological activities, such as cholagogic, hypoglycemic, antibacterial, and anti-inflammatory effects. The objective of this study was to investigate the effects of GIG on bile acid enterohepatic circulation and explore the underlying mechanism in cholestatic rats. Methods: In order to identify key pathways associated with cholestasis, we conducted Gene Ontology (GO) Enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. In vivo experiments were then performed on alpha-naphthylisothiocyanate (ANIT)-treated rats to assess the impact of GIG. We measured bile flow and various biomarkers including total bilirubin (TB), total bile acids (TBA), total cholesterol (TC), malondialdehyde (MDA), glutamic-pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), and total superoxide dismutase (T-SOD) in the serum. We also examined the expression levels of bile salt export pump (BSEP), ATP-binding cassette subfamily B member 4 (ABCB4), far-nesoid X receptor (FXR), small heterodimer partner (SHP), cholesterol 7α-hydroxylase (CYP7A1), and sodium taurocholate cotransporting polypeptide (NTCP) in liver tissue. In vitro experiments were conducted on primary hepatocytes to further investigate the mechanism of action of GIG on the expression of SHP, CYP7A1, NTCP, and FXR. Results: Our in vivo experiments demonstrated that GIG significantly increased bile flow and reduced the levels of TB, TBA, TC, MDA, GPT, and GOT, while increasing T-SOD levels in ANIT-treated rats. Addi-tionally, GIG ameliorated liver tissue damage induced by ANIT, upregulated the expression of BSEP and ABCB4, and modulated the protein expression of FXR, SHP, CYP7A1, and NTCP in model rats. In vitro experiments further revealed that GIG inhibited the expression of SHP, CYP7A1, and NTCP by suppressing the expression of FXR. Conclusion: This study provides new insights into the therapeutic potential of GIG for the treatment of cholestasis. GIG demonstrated beneficial effects on bile acid enterohepatic circulation and liver biomarkers in cholestatic rats. The modulation of FXR and its downstream targets may contribute to the mechanism of action of GIG. These findings highlight the potential of GIG as a therapeutic intervention for cholangitis.

Nocardia pseudobrasiliensis infection in a patient with arthritis.

Nocardia pseudobrasiliensis is a new taxon constituting an emerging species of human pathogenic Nocardia, which shares morphological features with N. brasiliensis. However, N. pseudobrasiliensis is more invasive and more easily disseminated, and it exhibits distinctive antibiotic susceptibility. Few clinical cases related to N. pseudobrasiliensis infection have been reported, and N. pseudobrasiliensis hydrarthrosis has not been described. Here, we analyzed the case information, diagnostic process, treatment, and prognosis of a patient with N. pseudobrasiliensis hydrarthrosis who received treatment in Zhejiang Provincial People's Hospital. Magnetic resonance imaging showed joint cavity effusion and soft tissue swelling with high signal on proton density-fat saturated images and low signal on T1-weighted images. Oil microscopy revealed abundant acid-fast-positive filaments in hydrarthrosis puncture fluid. The pathogen was identified as N. pseudobrasiliensis by matrix-assisted laser desorption ionization-time of flight mass spectrometry. In contrast to the 100% ciprofloxacin resistance displayed by N. brasiliensis, this clinical isolate of N. pseudobrasiliensis was completely susceptible. In summary, this is the first report of N. pseudobrasiliensis in joint effusion from a patient with arthritis.

Digital techniques and trends for seed phenotyping using optical sensors.

BACKGROUND: The breeding of high-quality, high-yield, and disease-resistant varieties is closely related to food security. The investigation of breeding results relies on the evaluation of seed phenotype, which is a key step in the process of breeding. In the global digitalization trend, digital technology based on optical sensors can perform the digitization of seed phenotype in a non-contact, high throughput way, thus significantly improving breeding efficiency. AIM OF REVIEW: This paper provides a comprehensive overview of the principles, characteristics, data processing methods, and bottlenecks associated with three digital technique types based on optical sensors: spectroscopy, digital imaging, and three-dimensional (3D) reconstruction techniques. In addition, the applicability and adaptability of digital techniques based on the optical sensors of maize seed phenotype traits, namely external visible phenotype (EVP) and internal invisible phenotype (IIP), are investigated. Furthermore, trends in future equipment, platform, phenotype data, and processing algorithms are discussed. This review offers conceptual and practical support for seed phenotype digitization based on optical sensors, which will provide reference and guidance for future research. KEY SCIENTIFIC CONCEPTS OF REVIEW: The digital techniques based on optical sensors can perform non-contact and high-throughput seed phenotype evaluation. Due to the distinct characteristics of optical sensors, matching suitable digital techniques according to seed phenotype traits can greatly reduce resource loss, and promote the efficiency of seed evaluation as well as breeding decision-making. Future research in phenotype equipment and platform, phenotype data, and processing algorithms will make digital techniques better meet the demands of seed phenotype evaluation, and promote automatic, integrated, and intelligent evaluation of seed phenotype, further helping to lessen the gap between digital techniques and seed phenotyping.

Varicella Zoster viral encephalitis without herpes: diagnosis by metagenomic next-generation sequencing of cerebrospinal fluid.

Acute Varicella Zoster viral encephalitis in immunocompetent adult patients without cutaneous herpes has rarely been reported. A 24-year-old female was hospitalized for a headache with a fever but without other obvious symptoms. Multiple routine examinations showed no abnormalities. Lumbar puncture indicated intracranial hypertension. The examination of cerebrospinal fluid by metagenomic next-generation sequencing demonstrated acute Varicella Zoster viral encephalitis. The patient's condition improved by treatment with acyclovir for antiviral therapy and mannitol dehydration to lower cranial pressure. Central Varicella Zoster viral infection should be emphasized as it is easily misdiagnosed and rare in clinical settings. Metagenomic next-generation sequencing of cerebrospinal fluid has significant advantages in the diagnosis of Varicella Zoster viral encephalitis.

Vectorized Evidential Learning for Weakly-Supervised Temporal Action Localization.

With the explosive growth of videos, weakly-supervised temporal action localization (WS-TAL) task has become a promising research direction in pattern analysis and machine learning. WS-TAL aims to detect and localize action instances with only video-level labels during training. Modern approaches have achieved impressive progress via powerful deep neural networks. However, robust and reliable WS-TAL remains challenging and underexplored due to considerable uncertainty caused by weak supervision, noisy evaluation environment, and unknown categories in the open world. To this end, we propose a new paradigm, named vectorized evidential learning (VEL), to explore local-to-global evidence collection for facilitating model performance. Specifically, a series of learnable meta-action units (MAUs) are automatically constructed, which serve as fundamental elements constituting diverse action categories. Since the same meta-action unit can manifest as distinct action components within different action categories, we leverage MAUs and category representations to dynamically and adaptively learn action components and action-component relations. After performing uncertainty estimation at both category-level and unit-level, the local evidence from action components is accumulated and optimized under the Subject Logic theory. Extensive experiments on the regular, noisy, and open-set settings of three popular benchmarks show that VEL consistently obtains more robust and reliable action localization performance than state-of-the-arts.

Integrating the atomically separated frontier molecular orbital distribution of two multiple resonance frameworks through a single bond for high-efficiency narrowband emission.

Atomically separated frontier molecular orbital (FMO) distribution plays a crucial role in achieving narrowband emissions for multiple resonance (MR)-type thermally activated delayed fluorescence emitters. Directly peripherally decorating a MR framework with donor or acceptor groups is a common strategy for developing MR emitters. However, this approach always induces bonding features and thus spectral broadening as a side effect. How direct donor/acceptor decoration enhances atomic FMO separation while avoiding bonding features has not been explored. For this aim, two MR derivatives are synthesized by integrating two MR frameworks at different sites. Following resonance alignment, DOBNA-m-CzBN avoids breaking nonbonding FMO features at the single connecting bond and shows enhanced MR characteristics, with a sharp emission at 491 nm and a full width at half maximum (FWHM) of 24 nm/118 meV. Conversely, DOBNA-p-CzBN emerges as a bonding feature due to its continuous π-conjugation extension, with a broadened FWHM of 26 nm/132 meV peaking at 497 nm. Impressively, both emitters exhibit outstanding external quantum efficiencies of 37.8-38.6% in organic light-emitting diodes (OLEDs), demonstrating improved performance with rigid acceptor decoration. Distinctly, the electroluminescence of DOBNA-m-CzBN shows a narrower FWHM than that of DOBNA-p-CzBN. This work for the first time reports the enhancement of atomic FMO separation for MR emitters via peripheral decoration through a single bond and provides a more comprehensive illustration for further development of MR emitters.

Uncertainty-Aware Dual-Evidential Learning for Weakly-Supervised Temporal Action Localization.

Weakly-supervised temporal action localization (WTAL) aims to localize the action instances and recognize their categories with only video-level labels. Despite great progress, existing methods suffer from severe action-background ambiguity, which mainly arises from background noise and neglect of non-salient action snippets. To address this issue, we propose a generalized evidential deep learning (EDL) framework for WTAL, called Uncertainty-aware Dual-Evidential Learning (UDEL), which extends the traditional paradigm of EDL to adapt to the weakly-supervised multi-label classification goal with the guidance of epistemic and aleatoric uncertainties, of which the former comes from models lacking knowledge, while the latter comes from the inherent properties of samples themselves. Specifically, targeting excluding the undesirable background snippets, we fuse the video-level epistemic and aleatoric uncertainties to measure the interference of background noise to video-level prediction. Then, the snippet-level aleatoric uncertainty is further deduced for progressive mutual learning, which gradually focuses on the entire action instances in an "easy-to-hard" manner and encourages the snippet-level epistemic uncertainty to be complementary with the foreground attention scores. Extensive experiments show that UDEL achieves state-of-the-art performance on four public benchmarks. Our code is available in github/mengyuanchen2021/UDEL.

Successful treatment with amoxicillin-clavulanic acid: cutaneous nocardiosis caused by Nocardia brasiliensis.

AIM: To emphasize the role of non-sulfonamides in the treatment of Nocardia infection and reduce the adverse reactions caused by sulfonamides. METHODS: We retrospectively analyzed a case of cutaneous nocardiosis in an immunocompetent individual. The colonies obtained by staining the pus in the lesion with antacid and culturing the agar plates were identified by flight mass spectrometry. The pathogenic identification showed Nocardia brasiliensis infection and the patient was treated with amoxicillin-clavulanic acid. RESULTS: After treatment with amoxicillin and clavulanic acid, the ulcer gradually peeled and crusted, leaving dark pigmentation. The patient has finally recovered. CONCLUSION: Sulfonamides are the first-line antibacterial agents for years in treatment of nocardiosis but are of great toxicity and side effects. This patient was successfully treated with amoxicillin-clavulanic acid and it provided a reference protocol for patients with sulfonamide-resistant Nocardia or sulfonamides intolerance.

Exosome-coated polydatin nanoparticles in the treatment of radiation-induced intestinal damage.

This study aimed to develop an exosome-coated polydatin (PD) nanoparticles (exo-PD) for improving the water solubility and bioavailability of polydatin and explore its salutary effects on intestinal radiation injury. Exosomes (exo) were extracted from the medium of human amniotic fluid stem cells (hAFSc). Mice were divided into control group, irradiation (IR) group, irradiation+PD (IR+PD) group, irradiation+exo (IR+exo) group and irradiation+exo-PD (IR+exo-PD) group. The results of characterization of protein markers, particle size, morphology and cellular uptake ability confirmed that exosomes were effectively isolated using ultracentrifugation. Compared with the IR group, exo-PD improved cell viability, prolonged survival of mice, improved leukocyte count and reduced diarrhea rate. Histological results showed that the exo-PD group had significant improvements in small intestinal villus length and crypt number and less crypt cell damage. exo-PD could reduce IL-1α and IL-6 levels, reduced γ-H2AX expression, increased mitochondrial membrane potential, enhanced oxidative phosphorylation, and delayed cellular senescence. exo-PD could alleviate intestinal injury by improving mitochondrial function through PI3K-AKT pathway. The exo-PD was able to reduce radiation damage to intestinal cells and could be a potential candidate for salvage of intestinal radiation damage.

Assessment of the Risk and Symptoms of SARS-CoV-2 Infection Among Healthcare Workers During the Omicron Transmission Period: A Multicentric Study from Four Hospitals of Mainland China.

Purpose: The SARS-CoV-2 omicron variant emerged and spread rapidly among the population in the early stage of China's normalized prevention and control in December 2022. Healthcare workers (HCWs) are particularly exposed to SARS-CoV-2, it is important to evaluate the impact of the omicron pandemic on HCWs in China. Methods: A self-administered online survey was conducted on infected HCWs from four hospitals of Taizhou. A total of 748 HCWs received the survey via DingTalk, and 328 responded to the questionnaire. The risk factors were investigated using univariate and multivariate logistic regression analysis. Results: By December 20, 2022, 748 HCWs tested positive by PCR, and the infection rate was 11.4% (748/6581). Among 328 respondents, the most common symptoms were cough (88.4%), fever (83.5%), runny nose (77.1%), sore throat (73.2%), headache (70.1%), muscle aches (67.1%), and fatigue (53.4%). 69.8% (229/328) of the participants had five or more major onset symptoms, while no severe case was observed. The multivariate analysis indicated that the poor sleep quality (OR = 2.29, 95% CI: 1.31-4.02, P = 0.004) was an independent risk factor for more major onset symptoms, while wore gloves ≥95% times in working (OR = 0.49, 95% CI: 0.28-0.85, P = 0.011) was significantly related to fewer symptoms. In addition, 239 (72.9%) recipients reported high fever (temperature ≥38.5°C), less common cold (≤3 vs >3 times/year, OR = 2.20, 95% CI: 1.05-4.65, P = 0.038) was significantly associated with high fever. Conclusion: Our findings imply rapid transmissibility of omicron and multiple-onset symptoms among HCWs. Improved autoimmunity and self-protection measures for HCWs may be helpful in controlling infection and clinical symptoms. Our results provide empirical reference values for improved countermeasures and protective measures for major public health emergencies.

Cadmium influence on lipid metabolism in Sprague-Dawley rats through linoleic acid and glycerophospholipid metabolism pathways.

Cadmium (Cd) is widely distributed in the environment and easy adsorbed by living organisms with adverse effects. Exposure to Cd-contaminated food may disrupt lipid metabolism and increase human health risk. To study the perturbation effect of Cd on lipid metabolism in vivo, 24 male Sprague-Dawley (SD) rats were randomly assigned four groups and treated by Cd chloride solution (0, 1.375 mg/kg, 5.5 mg/kg, 22 mg/kg) for 14 days. The characteristic indexes of serum lipid metabolism were analyzed. Afterwards, untargeted metabolomics analysis was applied to explore the adverse effects of Cd on rats by liquid chromatography coupled with mass spectrometry (LC-MS). The results revealed that Cd exposure obviously decreased the average serum of triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) and caused an imbalance of endogenous compounds in the 22 mg/kg Cd-exposed group. Compared with the control group, 30 metabolites with significant differences were identified in the serum. Our results indicated that Cd caused lipid metabolic disorders in rats by disrupting linoleic acid and glycerophospholipid metabolism pathways. Furthermore, there were three kinds of remarkable differential metabolites-9Z,12Z-octadecadienoic acid, PC(20:4(8Z,11Z,14Z,17Z)/0:0), and PC(15:0/18:2(9Z,12Z)), which enriched the two significant metabolism pathways and could be the potential biomarkers.