Laboratory diagnosis and treatment of Mycoplasma pneumoniae infection in children: a review.

Mycoplasma pneumoniae (MP) is the cause of Mycoplasma pneumoniae pneumonia (MPP) in children and adolescents, with the clinical manifestations highlighted by intermittent irritating cough, accompanied by headache, fever and muscle pain. This paper aimed to study the research status and focal points in MP infection, especially the common laboratory diagnostic methods and clinical treatment of Mycoplasma pneumoniae. Laboratory diagnostic methods include molecular assay, serological antibody detection, rapid antigen detection and isolation and culture. Polymerase chain reaction (PCR) is the gold standard with high sensitivity and specificity. The serological antibody can detect various immune antibodies qualitatively or quantitatively in serum. Rapid antigen can be detected faster, with no equipment environment requirements, which can be used for the early diagnosis of MP infection. While the culture growth cycle is long and insensitive, not recommended for routine diagnosis. Macrolides were the preferred drug for children with MPP, while the drug resistance rate was rising in China. Tetracycline can be substituted but was not recommended for children under 8 years of age, quinolone drugs are not necessary, severe MPP can be combined with glucocorticoids, involving the nervous or immune system can choose gamma globulin. Other treatments for MPP including symptomatic treatment which can alleviate symptoms, improve lung function and improve prognosis. A safe and effective vaccine needed to be developed which can provide protective immunity to children and will reduce the incidence of MPP.

Alternative Splicing Landscape of Head and Neck Squamous Cell Carcinoma.

Head and neck malignancies are a significant global health concern, with head and neck squamous cell carcinoma (HNSCC) being the sixth most common cancer worldwide accounting for > 90% of cases. In recent years, there has been growing recognition of the potential role of alternative splicing (AS) in the etiology of cancer. Increasing evidence suggests that AS is associated with various aspects of cancer progression, including tumor occurrence, invasion, metastasis, and drug resistance. Additionally, AS is involved in shaping the tumor microenvironment, which plays a crucial role in tumor development and response to therapy. AS can influence the expression of factors involved in angiogenesis, immune response, and extracellular matrix remodeling, all of which contribute to the formation of a supportive microenvironment for tumor growth. Exploring the mechanism of AS events in HNSCC could provide insights into the development and progression of this cancer, as well as its interaction with the tumor microenvironment. Understanding how AS contributes to the molecular changes in HNSCC cells and influences the tumor microenvironment could lead to the identification of new therapeutic targets. Targeted chemotherapy and immunotherapy strategies tailored to the specific AS patterns in HNSCC could potentially improve treatment outcomes and reduce side effects. This review explores the concept, types, processes, and technological advancements of AS, focusing on its role in the initiation, progression, treatment, and prognosis of HNSCC.

A Meta-analysis of Predicting Disorders of Consciousness After Traumatic Brain Injury by Machine Learning Models.

Objective: This study pursued a meta-analysis to evaluate the predictive accuracy of machine learning (ML) models in determining disorders of consciousness (DOC) among patients with traumatic brain injury (TBI). Methods: A comprehensive literature search was conducted to identify ML applications in the establishment of a predictive model of DOC after TBI as of August 6, 2023. Two independent reviewers assessed publication eligibility based on predefined criteria. The predictive accuracy was measured using areas under the receiver operating characteristic curves (AUCs). Subsequently, a random-effects model was employed to estimate the overall effect size, and statistical heterogeneity was determined based on I2 statistic. Additionally, funnel plot asymmetry was employed to examine publication bias. Finally, subgroup analyses were performed based on age, ML type, and relevant clinical outcomes. Results: Final analyses incorporated a total of 46 studies. Both the overall and subgroup analyses exhibited considerable statistical heterogeneity. Machine learning predictions for DOC in TBI yielded an overall pooled AUC of 0.83 (95% CI: 0.82-0.84). Subgroup analysis based on age revealed that the ML model in pediatric patients yielded an overall combined AUC of 0.88 (95% CI: 0.80-0.95); among the model subgroups, logistic regression was the most frequently employed, with an overall pooled AUC of 0.85 (95% CI: 0.83-0.87). In the clinical outcome subgroup analysis, the overall pooled AUC for distinguishing between consciousness recovery and consciousness disorders was 0.84 (95% CI: 0.82-0.85). Conclusion: The findings of this meta-analysis demonstrated outstanding accuracy of ML models in predicting DOC among patients with brain injuries, which presented substantial research value and potential of ML application in this domain.

Humoral immune responses primed by the alteration of gut microbiota were associated with galactose-deficient IgA1 production in IgA nephropathy.

Introduction: Galactose-deficient IgA1 (GdIgA1) is critical in the formation of immunodeposits in IgA nephropathy (IgAN), whereas the origin of GdIgA1 is unknown. We focused on the immune response to fecal microbiota in patients with IgAN. Methods: By running 16S ribosomal RNA gene sequencing, we compared IgAN samples to the control samples from household-matched or non-related individuals. Levels of plasma GdIgA1 and poly-IgA complexes were measured, and candidate microbes that can either incite IgA-directed antibody response or degrade IgA through specific IgA protease activities were identified. Results: The IgAN group showed a distinct composition of fecal microbiota as compared to healthy controls. Particularly, high abundance of Escherichia-Shigella was associated with the disease group based on analyses using receiver operating characteristic (area under curve, 0.837; 95% CI, 0.738-0.914), principle coordinates, and the linear discriminant analysis effect size algorithm (linear discriminant analysis score, 4.56; p < 0.001). Accordingly, the bacterial levels directly correlated with high titers of plasma GdIgA1(r = 0.36, p < 0.001), and patients had higher IgA1 against stx2(2.88 ± 0.46 IU/mL vs. 1.34 ± 0.35 IU/mL, p = 0.03), the main antigen of Escherichia-Shigella. Conversely, the healthy controls showed relatively higher abundance of the commensal bacteria that produce IgA-degrading proteases. Particularly, the abundance of some intestinal bacteria expressing IgA proteases showed an inverse correlation with the levels of plasma GdIgA1 in IgAN. Conclusion: Our data suggest that mucosal IgA production, including those of GdIgA1, is potentially linked to the humoral response to gut Escherichia-Shigella as one of the sources of plasma GdIgA1. Conversely, the IgA protease-producing microbiota in the gut are suppressed in patients with IgAN.

Ligilactobacillus salivarius XP132 with antibacterial and immunomodulatory activities inhibits horizontal and vertical transmission of Salmonella Pullorum in chickens.

Probiotics are increasingly recognized for their capacity to combat pathogenic bacteria. In this study, we isolated a strain of Ligilactobacillus salivarius XP132 from the gut microbiota of healthy chickens. This strain exhibited resistance to low pH and bile salts, auto-aggregation capabilities, and the ability to co-aggregate with pathogenic Salmonella. The in vitro antibacterial activity of Ligilactobacillus salivarius XP132 was tested using an Oxford cup antibacterial test, and the results showed that Ligilactobacillus salivarius XP132 exhibited broad-spectrum antibacterial activity, with especially strong antibacterial activity against Salmonella. In animal experiments with white feather broilers and specific-pathogens-free (SPF) chickens, we orally administered 1 × 109 CFU XP132 live bacteria per chicken per day, and detected the content of Salmonella in the liver, spleen, intestinal contents, and eggs of the chickens by RT-qPCR. Oral administration of Lactobacillus salivarius XP132 group significantly reduced the levels of Salmonella in chicken liver, spleen, intestinal contents and eggs, and the oral administration of Ligilactobacillus salivarius XP132 significantly inhibited the horizontal and vertical transmission of Salmonella in SPF chickens and white-feathered broilers. After oral administration of XP132, the production of chicken serum anti-infective cytokine IFN-γ was also significantly up-regulated, thereby enhancing the host's ability to resist infection. In addition, the production of various serum inflammatory cytokines, including IL-1ß, IL-6, IL-8, and TNF-α, was down-regulated, leading to significant amelioration of the inflammatory response induced by S. Pullorum in chickens. These findings suggest that Ligilactobacillus salivarius XP132 possesses potent antibacterial and immunomodulatory properties that effectively prevent both horizontal and vertical transmission of Salmonella Pullorum, highlighting its potential as a valuable tool for the prevention and control of Salmonella disease.

Uncovering the impact of metals on the formation and physicochemical properties of fat, oil and grease deposits in the sewer system.

The deposition of fats, oil, and grease (FOG) in sewers reduces conveyance capacity and leads to sanitary sewer overflows. The major contributing factor lies in the indiscriminate disposal of used cooking oil (UCO) via kitchen sinks. While prior investigations have mostly highlighted the significance of Ca2+ from concrete biocorrosion, the influence of common metal ions (e.g., Mg2+, Na+, K+) found in kitchen wastewater on FOG deposition has received limited attention in the existing literature. This study aimed to elucidate the roles of Ca, Mg, Na and K in FOG deposition in sewers and examine the influence of metal ions, fat/oil sources, and free fatty acids (FFAs) on the physicochemical and rheological properties of FOG deposits. To examine FOG deposit formation, synthetic wastewater containing 0.1 g/L of each metal ion was mixed with 40 mL of fat/oil and agitated for 8 h. Following FOG deposition, three distinct phases were observed: unreacted oil, FOG deposit and wastewater. The composition of these phases was influenced by the composition of metal ions and FFA in the wastewater. Mg produced the highest amount of FOG of 242.5 ± 10.6 mL compared to Ca (72.5 ± 3.5 mL) when each FFAs content in UCO was increased by 10 mg/mL. Molar concentration, valency and the solubility of metal ion sources were identified to influence the formation of FOG deposits via saponification and aggregation reaction. Furthermore, Fourier-Transform Infrared spectroscopy indicated that the FOG deposits in this study were similar to those collected from the field. This study showed that the use of Mg(OH)2 as a biocorrosion control measure would increase FOG deposition and highlights the need for a comprehensive understanding of its roles in real sewage systems.

Early predictive values of clinical assessments for ARDS mortality: a machine-learning approach.

Acute respiratory distress syndrome (ARDS) is a devastating critical care syndrome with significant morbidity and mortality. The objective of this study was to evaluate the predictive values of dynamic clinical indices by developing machine-learning (ML) models for early and accurate clinical assessment of the disease prognosis of ARDS. We conducted a retrospective observational study by applying dynamic clinical data collected in the ARDSNet FACTT Trial (n = 1000) to ML-based algorithms for predicting mortality. In order to compare the significance of clinical features dynamically, we further applied the random forest (RF) model to nine selected clinical parameters acquired at baseline and day 3 independently. An RF model trained using clinical data collected at day 3 showed improved performance and prognostication efficacy (area under the curve [AUC]: 0.84, 95% CI: 0.78-0.89) compared to baseline with an AUC value of 0.72 (95% CI: 0.65-0.78). Mean airway pressure (MAP), bicarbonate, age, platelet count, albumin, heart rate, and glucose were the most significant clinical indicators associated with mortality at day 3. Thus, clinical features collected early (day 3) improved performance of integrative ML models with better prognostication for mortality. Among these, MAP represented the most important feature for ARDS patients' early risk stratification.

Analysis of microbial communities in wheat, alfalfa, and oat crops after Tilletia laevis Kühn infection.

Common bunt caused by Tilletia laevis Kühn is one of the most serious fungal diseases of wheat. The root-microbial associations play key roles in protecting plants against biotic and abiotic factors. Managing these associations offers a platform for improving the sustainability and efficiency of agriculture production. Here, by using high throughput sequencing, we aimed to identify the bacterial and fungal associations in wheat, alfalfa, and oat crops cultivated in different years in the Gansu province of China. Soil samples (0-6 cm below the surface) from infected wheat by T. laevis had significantly more bacterial and fungal richness than control samples as per the Chao1 analysis. We found some dominant fungi and bacterial phyla in infected wheat by T. laevis, such as Proteobacteria, Acidobacteria, Actinobacteria, Chloroflexi, Ascomycota, Basidiomycota, and Mortierello mycota. We also analyzed the chemical and enzymatic properties of soil samples after T. laevis inoculation. The total nitrogen, total kalium (TK), ammonium nitrogen, available kalium, organic carbon, invertase, phosphatase, and catalase were more in T. laevis-infected samples as compared to the control samples, while pH, total phosphorus, nitrate nitrogen, available phosphorus, and urease were more in control samples compared to T. laevis-infected samples. The results of this study will contribute to the control of wheat common bunt by candidate antagonistic microorganisms and adverse properties of soil.

Isoliensinine activated the Nrf2/GPX4 pathway to inhibit glutamate-induced ferroptosis in HT-22 cells.

Isoliensinine (ISO), a natural compound, is a bibenzyl isoquinoline alkaloid monomer in lotus seed, which has strong antioxidant and free radical scavenging activities. The oxidative toxicity caused by glutamic acid overdose is one of the important mechanisms of nerve cell injury, and the oxidative toxicity caused by glutamic acid is related to ferroptosis. This study aims to establish a glutamate-induced injury model of mouse hippocampal neurons HT-22 cells, and investigate the protective effect of ISO on the neurotoxicity of glutamate-induced HT-22 cells. The results showed that ISO inhibited glutamate-induced ferroptosis of neuronal cells through nuclear factor E2-related factor 2/glutathione peroxidase 4 (Nrf2/GPX4) signaling pathway. Pretreatment of HT-22 cells with ISO significantly reduced glutamate-induced cell death. Ferroptosis inhibitors have the same effect. ISO inhibited the decrease of mitochondrial membrane potential detection and the increase of iron content induced by glutamate, the increase of malondialdehyde and reactive oxygen species in cytoplasm and lipid, and protected the activities of GPx and superoxide dismutase enzymes. In addition, WB showed that glutamic acid could induce the upregulated expression of long-chain esteryl coA synthase 4 (ACSL4) protein and the downregulated expression of SLC7A11 and GPX4 protein in HT-22 cells, while ISO could prevent the abnormal expression of these proteins induced by glutamic acid. The nuclear translocation of Nrf2 in HT-22 cells was increased, and the expression of downstream heme oxygenase-1 protein was upregulated. In summary, ISO protects HT-22 cells from glutamate-induced ferroptosis through a novel mechanism of the Nrf2/GPX4 signaling pathway.

Human exposure risk of organic UV filters: A comprehensive analysis based on primary exposure pathways.

The exposure of organic UV filters has been increasingly confirmed to induce adverse effects on humans. However, the critical exposure pathway and the vulnerable population of organic UV filters are not clearly identified. This paper attempts to evaluate the health risk of commonly used organic UV filters from various exposure routes based on comprehensive analysis strategy. The estimated daily intakes (EDI) and hazard quotient (HQ) values of organic UV filters through four pathways (dermal exposure, indoor dust, indoor air, and drinking water) for various age groups were determined. Although the total HQ values (0.01-0.4) from comprehensive exposure of organic UV filters were below risk threshold (1.0), infants were identified as the most vulnerable population, with EDI (75.71 ng/kg-bw/day) of 2-3 times higher than that of adults. Additionally, the total EDI values of individual exposure pathways were estimated and ranked as follows: indoor air (138.44 ng/kg-bw/day) > sunscreen application (37.2 ng/kg-bw/day) > drinking water (21.87 ng/kg-bw/day) > indoor dust (9.24 ng/kg-bw/day). Moreover, we successfully tailored the Sankey diagram to depict the EDI proportion of individual organic UV filters from four exposure pathways. It was noted that EHMC (ethylhexyl methoxycinnamate) and EHS (ethylhexyl salicylate) dominated the contribution of EDI (72 %) via indoor air exposure routes. This study serves as a crucial reference for enhancing public health risk awareness concerning organic UV filters, with a special focus on the vulnerable populations such as infants and children.

Luteolin-7-diglucuronide, a novel PTP1B inhibitor, ameliorates hepatic stellate cell activation and liver fibrosis in mice.

Liver fibrosis, one of the leading causes of morbidity and mortality worldwide, lacks effective therapy. The activation of hepatic stellate cells (HSCs) is the dominant event in hepatic fibrogenesis. Luteolin-7-diglucuronide (L7DG) is the major flavonoid extracted from Perilla frutescens and Verbena officinalis. Their beneficial effects in the treatment of liver diseases were well documented. In this study we investigated the anti-fibrotic activities of L7DG and the potential mechanisms. We established TGF-ß1-activated mouse primary hepatic stellate cells (pHSCs) and human HSC line LX-2 as in vitro liver fibrosis models. Co-treatment with L7DG (5, 20, 50 µM) dose-dependently decreased TGF-ß1-induced expression of fibrotic markers collagen 1, α-SMA and fibronectin. In liver fibrosis mouse models induced by CCl4 challenge alone or in combination with HFHC diet, administration of L7DG (40, 150 mg·kg-1·d-1, i.g., for 4 or 8 weeks) dose-dependently attenuated hepatic histopathological injury and collagen accumulation, decreased expression of fibrogenic genes. By conducting target prediction, molecular docking and enzyme activity detection, we identified L7DG as a potent inhibitor of protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 2.10 µM. Further studies revealed that L7DG inhibited PTP1B activity, up-regulated AMPK phosphorylation and subsequently inhibited HSC activation. This study demonstrates that the phytochemical L7DG may be a potential therapeutic candidate for the treatment of liver fibrosis.

Synergistic effects of bivalve and microalgae co-cultivation on carbon dynamics and water quality.

Aquaculture of bivalve shellfish and algae offers significant ecological benefits, yet the complex interactions between these organisms can substantially impact local carbon dynamics. This study investigated the effects of co-culturing four intertidal bivalve species Pacific oysters (Crassostrea gigas), Manila clams (Ruditapes philippinarum), Chinese clams (Cyclina sinensis), and hard clams (Mercenaria mercenaria) with microalgae (Isochrysis galbana) on specific water quality parameters, including total particulate matter (TPM), total organic matter (TOM), dissolved inorganic carbon (DIC), dissolved carbon dioxide (dCO2), dissolved oxygen (DO), and ammonium (NH4+) concentrations. The bivalves were divided into smaller and larger groups and cultured under two conditions: with algae (WP) and without (NP), along with matched controls. Total particulate matter (TPM), total organic matter (TOM), dissolved oxygen (DO), ammonium nitrogen (NH4+), dissolved inorganic carbon (DIC), and CO2 (dCO2) were measured before and after 3-h cultivation. Results revealed species-specific impacts on water chemistry. C. gigas, C. sinensis and R. philippinarum showed the strongest reduction in DIC and dCO2 in WP groups, indicating synergistic bioremediation with algae. M. mercenaria notably reduced TPM, highlighting its particle carbon sequestration potential. DO concentrations decreased in most WP or NP groups, reflecting respiration of the cultured bivalves or microalgae. NH4+ levels also declined for most species, indicating nitrogen assimilation by these creatures. Overall, the bivalve size significantly impacted carbon and nitrogen processing capacities. These findings reveal species-specific capabilities in regulating water carbon dynamics. Further research should explore integrating these bivalves in carbon-negative aquaculture systems to mitigate environmental impacts. This study provides valuable insights underlying local carbon dynamics in shallow marine ecosystems.

Structural characterization and immune activity evaluation of a polysaccharide from Lyophyllum Decastes.

An innovative acidic hydrolysate fingerprinting workflow was proposed for the characterization of Lyophyllum Decastes polysaccharide (LDP) by ultra performance liquid chromatography-mass spectrometry (UPLC-MS). The crude polysaccharides were firstly separated and purified by using DE-52 column and the BRT GPC purification system, respectively. The molecular weight and monosaccharide content of homogeneous polysaccharides were ascertained by utilizing HPGPC and ion chromatography separately. Secondly, the linkage of LDP was identified by methylation analysis and 1D/2D NMR spectra. The UPLC-MS/MS was used to scan and identify the acidic hydrolysate products of LDP using the PGC column. The oligosaccharides were collected by chromatography and identified by mass spectrometry. Thirdly, the expression of IL-1, IL-6, iNOS, TNF-α and IFNAR-I was measured in order to assess the immunological activity of LDP. Besides, the targeted receptors identification of polysaccharides was performed by screening the expression of TLRs family protein. The results showed that oligosaccharide fragments with different molecular weights can be obtained by partial hydrolysis, which further verified that the structures of LDP polysaccharides was a 1-6-linked ß-glucan. Moreover, the LDP polysaccharide can up-regulate the content of IL-1ß, IL-6, iNOS, TNF-α and IFNAR-I and plays an important immunoregulation role through TLRs family.

A novel prognostic nomogram based on imaging and molecular parameters for newly diagnosed extranodal natural killer/T-cell lymphoma patients.

Not available.

Type 2 herpes simplex virus-induced anti-N-methyl-D-aspartate receptor encephalitis responsive to immunoglobulin monotherapy.

Herpes simplex virus-2 encephalitis (HSV2E) in immunocompetent adults is exceptionally rare, and the subsequent onset of autoimmune encephalitis after HSV2E is even less common. This report presents the inaugural Chinese case of anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) induced by HSV2E, confirmed via metagenomic next-generation sequencing (mNGS). The patient demonstrated a favorable response to intravenous immunoglobulin (IVIG) monotherapy. This case emphasizes the importance of considering autoimmune encephalitis in patients exhibiting new or recurrent neurological symptoms after HSV2E recovery. Comprehensive mNGS and neuronal antibody testing are essential for timely diagnosis. Moreover, IVIG monotherapy can serve as an effective treatment for NMDARE induced by HSV2, providing a viable alternative, particularly when steroid therapy is contraindicated.

Microbiological characteristics of the lower airway in adults with bronchiectasis: a prospective cohort study.

BACKGROUND: Microbial infection and colonization are frequently associated with disease progression and poor clinical outcomes in bronchiectasis. Identification of pathogen spectrum is crucial for precision treatment at exacerbation of bronchiectasis. METHODS: We conducted a prospective cohort study in patients with bronchiectasis exacerbation onset and stable state. Bronchoalveolar lavage fluid (BALF) was collected for conventional microbiological tests (CMTs) and metagenomic Next-Generation Sequencing (mNGS). Bronchiectasis patients were monitored for documenting the time to the next exacerbation during longitudinal follow-up. RESULTS: We recruited 168 eligible participants in the exacerbation cohorts, and 38 bronchiectasis patients at stable state at longitudinal follow-up. 141 bronchiectasis patients at exacerbation onset had definite or probable pathogens via combining CMTs with mNGS reports. We identified that Pseudomonas aeruginosa, non-tuberculous mycobacteria, Haemophilus influenzae, Nocardia spp, and Staphylococcus aureus were the top 5 pathogens with a higher detection rate in our cohorts via combination of CMTs and mNGS analysis. We also observed strong correlations of Pseudomonas aeruginosa, Haemophilus influenzae, non-tuberculous mycobacteria with disease severity, including the disease duration, Bronchiectasis Severity Index, and lung function. Moreover, the adjusted pathogenic index of potential pathogenic microorganism negatively correlated (r = -0.7280, p < 0.001) with the time to the next exacerbation in bronchiectasis. CONCLUSION: We have revealed the pathogenic microbial spectrum in lower airways and the negative correlation of PPM colonization with the time to the next exacerbation in bronchiectasis. These results suggested that pathogens contribute to the progression of bronchiectasis.

The de novo missense mutation F224S in GABRB2, identified in epileptic encephalopathy and developmental delay, impairs GABAAR function.

Genetic variants in genes encoding subunits of the γ-aminobutyric acid-A receptor (GABAAR) have been found to cause neurodevelopmental disorders and epileptic encephalopathy. In a patient with epilepsy and developmental delay, a de novo heterozygous missense mutation c.671 T > C (p.F224S) was discovered in the GABRB2 gene, which encodes the ß2 subunit of GABAAR. Based on previous studies on GABRB2 variants, this new GABRB2 variant (F224S) would be pathogenic. To confirm and investigate the effects of this GABRB2 mutation on GABAAR channel function, we conducted transient expression experiments using GABAAR subunits in HEK293T cells. The GABAARs containing mutant ß2 (F224S) subunit showed poor trafficking to the cell membrane, while the expression and distribution of the normal α1 and γ2 subunits were unaffected. Furthermore, the peak current amplitude of the GABAAR containing the ß2 (F224S) subunit was significantly smaller compared to the wild type GABAAR. We propose that GABRB2 variant F224S is pathogenic and GABAARs containing this ß2 mutant reduce response to GABA under physiological conditions, which could potentially disrupt the excitation/inhibition balance in the brain, leading to epilepsy.

Methods and applications of noncompetitive hapten immunoassays.

Hapten immunoassays have found extensive application across various domains such as disease diagnostics, environmental monitoring, as well as the evaluation of food and pharmaceutical safety. These techniques traditionally rely on competitive assay formats and often face challenges with sensitivity and specificity. This review focuses on the emergent noncompetitive immunoassay technologies that promise to transcend these limitations through innovative approaches. Noncompetitive immunoassays, leveraging novel elements such as anti-idiotype antibodies, anti-immunocomplex (IC) antibodies, and the strategic use of nanomaterial-enhanced signal detection, are setting new benchmarks for analytical performance. These advancements not only enhance the detection capabilities but also significantly improve specificity inherent in traditional methods. Moreover, the integration of novel materials and binding reagents in these assays offers substantial improvements in assay dynamics, providing faster, more accurate, and reliable results. This review consolidates the latest methodologies and their applications, underlining the transformative impact of noncompetitive technologies in the sensitive detection of haptens across various fields.

Baló's concentric sclerosis with spontaneous remission and favorable prognosis.

Introduction: Baló's concentric sclerosis (BCS) is a rare type of central nervous system demyelinating disorder. Most patients with BCS are treated with corticosteroids, and spontaneous remission has seldom been described. Case presentation: A 46-year-old man presented with a subacute-onset headache and memory loss. Brain magnetic resonance imaging (MRI) revealed multiple onion-shaped ring lesions with mild enhancement in the outermost ring. A brain biopsy revealed significant myelin loss. The diagnosis of BCS was established based on the MRI results and pathological findings. Interestingly, the patient recovered almost completely without immunotherapy, with repeated brain MRI at the 1-year follow-up showing an obvious reduction in the extent of the lesions. Conclusion: Neurologists should improve the recognition of the typical MRI features of BCS to avoid unnecessary biopsies. Although rare, spontaneous remission can be observed in clinical practice.

Dihydroisotanshinone I regulates ferroptosis via PI3K/AKT pathway to enhance cisplatin sensitivity in lung adenocarcinoma.

OBJECTIVES: Dihydroisotanshinone I (DT) is a kind of diterpenoid compound extracted from the dried roots of Salvia miltiorrhiza Bunge, and exhibits multiple biological activities including anti-tumor activity. Cisplatin is one of the first-line drugs for the treatment of lung adenocarcinoma (LAUD), but the drug resistance and toxicity limit its efficacy. DT is known to induce apoptosis and ferroptosis, but it is unclear whether DT can inhibit the cisplatin-resistant LAUD cells and reverse the drug resistance in LAUD. Therefore, our study intends to establish the cisplatin-resistant human LAUD cells (A549/DDP), and figure out the influence and related mechanisms of DT reversing cisplatin resistance in A549/DDP cells, so as to provide a theoretical basis for the DT as a new natural candidate for the treatment of LAUD. METHODS: The establishment of A549/DDP was the continuous stimulation by exposing A549 to gradient concentrations of Cisplatin. The cell viability of A549 and A549/DDP was detected by CCK-8 kit, and the IC50 value was calculated. The morphological changes of A549 and A549/DDP cells were observed by an inverted microscope. The contents of malondialdehyde (MDA) and glutathione (GSH) in A549/DDP cells after drug treatment were detected by related kits. The levels of Fe2+, cytosolic reactive oxygen species (ROS), and lipid reactive oxygen species (lipid ROS) were detected by a fluorescence microplate reader or fluorescence cell imager according to the related fluorescent probe kit instructions. Western blot was used to detect the expressions of PI3K, phospho-PI3K, AKT, phospho-AKT, MDM2, p53, GPX4, and SLC7A11 in A549/DDP after different drug treatments. KEY FINDINGS: Our study demonstrated that the inhibitory effect of DT on A549 and A549/DDP cells was time-dependent and concentration-dependent, and DT and DDP had a synergistic effect on inhibiting the proliferation of A549/DDP cells. Furthermore, DT mainly induced ferroptosis in A549/DDP cells and synergized with cisplatin to promote ferroptosis in A549/DDP cells. The result of KEGG pathway analysis, molecular docking and western blot showed that DT could enhance the cisplatin sensitivity of A549/DDP by inhibiting PI3K/MDM2/P53 signaling pathway. CONCLUSIONS: Consequently, we concluded that DT promotes ferroptosis in cisplatin-resistant LAUD A549/DDP cells. Additionally, DT reverses cisplatin resistance by promoting ferroptosis via PI3K/MDM2/P53 pathway in A549/DDP cells.