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Background: Linezolid (LZD) is a cornerstone medication in the treatment of drug-resistant tuberculosis (DR-TB). However, it frequently triggers adverse effects such as bone marrow suppression, optic neuropathy, and peripheral neuropathy, all of which can impact treatment outcomes and prognosis. Contezolid (CZD), a novel oxazolidinone antibiotic, exhibits comparable antimicrobial efficacy against Mycobacterium tuberculosis as LZD, but with potentially enhanced safety profiles. Case Presentation: This report presents five cases (Cases 1-5) of LZD intolerance, wherein CZD served as an effective alternative treatment. In Cases 1-3, LZD administration resulted in bone marrow suppression, primarily manifested as anemia. Transitioning to CZD therapy led to a rise and stabilization of hemoglobin (HGB) levels in Cases 1-2, and a return to baseline values in Case 3. In Case 4, CZD treatment alleviated symptoms of LZD-induced peripheral neuritis, although complete resolution was not achieved, hinting at potential irreversibility of this type of peripheral neuropathy. In Case 5, direct CZD anti-TB therapy was initiated for recurrent leukopenia and neutropenia, resulting in no further severe myelosuppression and successful recovery. Conclusion: These case studies suggest that CZD could represent an effective and safe option for anti-TB therapy, especially for patients intolerant to LZD.
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Stem cells, with their ability to self-renew and differentiate into various cell types, are a unique and valuable resource for medical research and toxicological studies. The liver is the most crucial metabolic organ in the human body and serves as the primary site for the accumulation of environmental pollutants. Enrichment with environmental pollutants can disrupt the early developmental processes of the liver and have a significant impact on liver function. The liver comprises a complex array of cell types, and different environmental pollutants have varying effects on these cells. Currently, there is a lack of well-established research models that can effectively demonstrate the mechanisms by which environmental pollutants affect human liver development. The emergence of liver cells and organoids derived from stem cells offers a promising tool for investigating the impact of environmental pollutants on human health. Therefore, this study systematically reviewed the developmental processes of different types of liver cells and provided an overview of studies on the developmental toxicity of various environmental pollutants using stem cell models.
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Graphite exhibits crystal anisotropy, which impedes the mass transfer of ion intercalation and extraction processes in Li-ion batteries. Herein, a dual-shock chemical strategy has been developed to synthesize the carbon anode. This approach comprised two key phases: (1) a thermal shock utilizing ultrahigh temperature (3228 K) can thermodynamically facilitate graphitization; (2) a mechanical shock (21.64 MPa) disrupting the π-π interactions in the aromatic chains of carbon can result in hybrid-structured carbon composed of crystalline and amorphous carbon. The optimized carbon (DSC-200-0.3) demonstrates a capacity of 208.61 mAh/g at a 10C rate, with a significant enhancement comparing with 15 mAh/g of the original graphite. Impressively, it maintains 81.06% capacity even after 3000 charge-discharge cycles. Dynamic process analysis reveals that this superior rate performance is attributed to a larger interlayer spacing facilitating ion transport comparing with the original graphite, disordered amorphous carbon for additional lithium storage sites, and crystallized carbon for enhanced charge transfer. The dual-shock chemical approach offers a cost-effective and efficient method to rapidly produce hybrid-structured carbon anodes, enabling 10C fast charging capabilities in lithium-ion batteries.
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The low initial Coulombic efficiency (ICE) greatly hinders the practical application of MXenes in sodium-ion batteries. Herein, theoretical calculations confirm that -F and -OH terminations as well as the tetramethylammonium ion (TMA+) intercalator in sediment Ti3C2Tx (s-Ti3C2Tx) MXene possess strong interaction with Na+, which impedes Na+ desorption during the charging process and results in low ICE. Consequently, Na+-intercalated sediment Ti3C2Tx (Na-s-Ti3C2Tx) is constructed through Na2S·9H2O treatment of s-Ti3C2Tx. Specifically, Na+ can first exchange with TMA+ of s-Ti3C2Tx and then combine with -F and -OH terminations, thus leading to the elimination of TMA+ and preshielding of -F and -OH. As expected, the resulting Na-s-Ti3C2Tx anode delivers considerably boosted ICE values of around 71% in carbonate-based electrolytes relative to s-Ti3C2Tx. Furthermore, electrolyte optimization is employed to improve ICE, and the results demonstrate that an ultrahigh ICE value of 94.0% is obtained for Na-s-Ti3C2Tx in the NaPF6-diglyme electrolyte. More importantly, Na-s-Ti3C2Tx exhibits a lower Na+ migration barrier and higher electronic conductivity compared with s-Ti3C2Tx based on theoretical calculations. In addition, the cyclic stability and rate performance of the Na-s-Ti3C2Tx anode in various electrolytes are comprehensively explored. The presented simple strategy in boosting ICE significantly enhances the commercialization prospect of MXenes in advanced batteries.
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Nanoparticles have unique properties that make them useful in biomedicine. However, their extensive use raises concerns about potential hazards to the body. Therefore, it is crucial to establish effective and robust toxicology models to evaluate the developmental and functional toxicity of nanoparticles on the body. This article discusses the use of stem cells to study the developmental and functional toxicity of organs of endodermal origin due to nanoparticles. The study discovered that various types of nanoparticles have varying effects on stem cells. The application of stem cell models can provide a possibility for studying the effects of nanoparticles on organ development and function, as they can more accurately reflect the toxic mechanisms of different types of nanoparticles. However, stem cell toxicology systems currently cannot fully reflect the effects of nanoparticles on entire organs. Therefore, the establishment of organoid models and other advanced assessment models is expected to address this issue.
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Endodermo , Nanopartículas , Células Madre , Animales , Nanopartículas/toxicidad , Humanos , Células Madre/efectos de los fármacos , Endodermo/efectos de los fármacos , Endodermo/citologíaRESUMEN
Inflammatory cytokines have crucial roles in the pathogenesis of tuberculosis (TB), and interleukin (IL)-27 and IL-35 have a pro-inflammatory and anti-inflammatory effect on many diseases, including infectious diseases. Therefore, we evaluated the relationship between IL-27 and IL-35 gene polymorphism, expression levels, and pulmonary TB (PTB) susceptibility. Nine single-nucleotide polymorphisms (SNPs) in the IL-27 gene (rs181206, rs153109, and rs17855750) and the IL-35 gene (rs4740, rs428253, rs9807813, rs2243123, rs2243135, and rs568408) were genotyped by the SNPscan technique in 497 patients with PTB and 501 controls. There was no significant difference regarding the genotype and allele frequencies of the above SNPs in the IL-27 and IL-35 genes between patients with PTB and controls. Haplotype analysis showed that the frequency of the GAC haplotype in the IL-35 gene was significantly decreased in patients with PTB when compared to controls (p = 0.036). Stratified analysis suggested that the frequency of the IL-27 rs17855750 GG genotype was significantly increased in patients with PTB with fever. Moreover, the lower frequency of the IL-35 rs568408 GA genotype was associated with drug-induced liver injury in patients with PTB. The IL-35 rs428253 GC genotype, as well as the rs4740 AA genotype and A allele, showed significant relationships with hypoproteinemia in patients with PTB. When compared with controls, the IL-27 level was significantly increased in patients with PTB. Taken together, IL-35 gene variation might contribute to a protective role on the susceptibility to PTB, and IL-27 and IL-35 gene polymorphisms were associated with several clinical manifestations of patients with PTB.
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Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Interleucinas , Polimorfismo de Nucleótido Simple , Tuberculosis Pulmonar , Humanos , Interleucinas/genética , Masculino , Femenino , Tuberculosis Pulmonar/genética , Adulto , Persona de Mediana Edad , Genotipo , Haplotipos , Estudios de Casos y Controles , Alelos , Interleucina-27/genéticaRESUMEN
This study explored the effects of different vitamin B5 (VB5) levels on intestinal growth and function of weaned piglets. Twenty-one piglets (7.20 ± 1.11 kg) were included in a 28-day feeding trial with three treatments, including 0 mg/kg (L-VB5), 10 mg/kg (Control) and 50 mg/kg (H-VB5) of VB5 supplement. The results showed that: Large intestine weight/body weight was the highest in H-VB5 group, Control and H-VB5 groups had significantly higher villus height and villus height/crypt depth than the L-VB5 in the ileum (p < .05). Goblet cells (ileal crypt) and endocrine cells (ileal villus) significantly increased in Control and H-VB5 (p < .05). The H-VB5 group exhibited significantly higher levels of ki67 and crypt depth in the cecum and colon, colonic goblet cells and endocrine cells were both rising considerably (p < .05). Isobutyric acid and isovaleric acid were significantly reduced in the H-VB5 group (p < .05), and there was a decreasing trend in butyric acid (p = .073). At the genus level, the relative abundance of harmful bacteria such as Clostridium_Sensu_Structo_1 Strecto_1, Terrisporbacter and Streptococcus decreased significantly and the relative abundance of beneficial bacteria Turicibacter increased significantly in H-VB5 group (p < .05). Overall, the addition of 50 mg/kg VB5 primarily enhanced the morphological structure, cell proliferation and differentiation of the ileum, cecum and colon. It also had a significant impact on the gut microbiota and short-chain fatty acids.
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Ciego , Ácido Pantoténico , Animales , Ácido Butírico , Diferenciación Celular , Suplementos Dietéticos , PorcinosRESUMEN
Background: A high rate of glomerulosclerosis serves as an important signal of poor response to treatment and a high risk of disease progression or adverse prognosis in transplanted kidneys. We hypothesized that contrast-enhanced ultrasound (CEUS) could serve as a novel imaging biomarker in the early prediction of glomerulosclerosis rate by evaluating renal allograft microcirculation. Methods: A retrospective analysis was performed on 143 transplanted kidney recipients with confirmed pathology, including 100 in the training group and 43 in the validation group. All patients underwent conventional ultrasound (CUS) and CEUS examinations. The patients were divided into two groups: those with >50% glomerulosclerosis and those with ≤50% glomerulosclerosis. The nomograms derived from independent predictors identified by multivariate logistic analysis were assessed using receiver operating characteristic (ROC) curve analysis, 1,000 bootstrap resamples, calibration curves, and decision curve analysis (DCA). Results: The patients with >50% glomerulosclerosis and those with ≤50% glomerulosclerosis showed statistically significant differences in CEUS parameters, including in peak intensity (PI) (25 vs. 30; P<0.001), absolute time to peak (ATTP) (10 vs. 9; P=0.004), and time to peak (TTP) (22 vs. 19.5; P=0.026). Multivariate analysis revealed that PI [odds ratio (OR) =0.852; 95% confidence interval (CI): 0.737-0.986], peak systolic velocity (PSV) of the interlobar artery (OR =0.850; 95% CI: 0.758-0.954), cortical echogenicity (OR =38.429; 95% CI: 3.695-399.641), and time since transplantation (OR =1.017; 95% CI: 1.006-1.028) were independent predictors of whether the glomerulosclerosis rate was >50% and were incorporated into the construction of a nomogram. The area under the curve (AUC) of the nomogram in the training and validation groups was 0.914 (95% CI: 0.840-0.960) and 0.909 (95% CI: 0.781-0.975), respectively, with a bootstrap resampling AUC of 0.877. The calibration curve and DCA confirmed the diagnostic performance of the nomogram model. Conclusions: The nomogram, which combined CUS, CEUS, and clinical indicators, exhibited notable predictive efficacy for the glomerulosclerosis rate in transplanted kidneys, thereby demonstrating the potential to improve clinical decision-making.
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OBJECTIVE: Intestinal ultrasound (IUS) is an emerging modality for assessing disease activity, extent, and treatment response in ulcerative colitis. This study aimed to evaluate the potential of IUS in predicting severe flares, the need for rescue therapy (corticosteroid failure), and colectomy in patients with ulcerative colitis. METHODS: We conducted a retrospective review of medical records, collecting clinical and IUS data. The Milan Ultrasound Criteria (MUC) score was used to assess ulcerative colitis severity. Group comparisons were performed to identify differences in MUC scores between mild-to-moderate and severe ulcerative colitis, between steroid responders and nonresponders, and between patients who underwent colectomy and those who did not. Receiver operating characteristic (ROC) analysis was used to predict outcomes in patients with ulcerative colitis. RESULTS: This analysis included 102 patients with ulcerative colitis categorized as mild/moderate (60) or severe (42). MUC scores were significantly higher in the severe ulcerative colitis group compared with the mild/moderate group ( P â <â 0.001). Analysis (using ROC) identified a cutoff MUC score of >8.54 to indicate severe ulcerative colitis with good sensitivity (64.29%) and excellent specificity (93.33%). Similarly, a cutoff of MUCâ >â 10.54 showed promise in predicting corticosteroid failure, with acceptable sensitivity (50%) and high specificity (90.91%). Finally, a cutoff MUC score >12.5 demonstrated potential for predicting colectomy, exhibiting moderate sensitivity (55.56%) but excellent specificity (96.97%). CONCLUSION: IUS may be useful for differentiating severe ulcerative colitis from mild-to-moderate disease, identifying early stage failure of corticosteroid therapy, and predicting the potential need for colectomy.
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Corticoesteroides , Colectomía , Colitis Ulcerosa , Valor Predictivo de las Pruebas , Curva ROC , Índice de Severidad de la Enfermedad , Insuficiencia del Tratamiento , Ultrasonografía , Humanos , Colitis Ulcerosa/cirugía , Colitis Ulcerosa/diagnóstico por imagen , Colitis Ulcerosa/tratamiento farmacológico , Masculino , Femenino , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Corticoesteroides/uso terapéutico , Adulto Joven , Medición de Riesgo , AncianoRESUMEN
2-Aminobenzothiazoles are commonly encountered in various functional compounds. Herein, we disclose an electro-oxidative three-component reaction for the effective synthesis of 2-aminobenzothiazoles under mild conditions, utilizing non-toxic and abundant elemental sulfur as the sulfur source. Both aliphatic amines and aryl amines demonstrate good compatibility at room temperature, highlighting the broad functional group tolerance of this approach. Additionally, elemental selenium demonstrated reactivities comparable to those of elemental sulfur.
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Phenazines, crucial constituents of nitrogen-containing heterocycles, widely exist in functional compounds. Herein, we report an anodic oxidative (4 + 2) cyclization between anilines and o-phenylenediamines for the uniform construction of phenazines in a simple undivided cell. Dual C-H amination followed by oxidation represents an outstanding step and atom efficiency. A sequence of phenazines is produced with excellent functional group tolerance at room temperature.
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The global incidence rate of kidney cancer (KC) has been steadily increasing over the past 30 years. With the aging global population, kidney cancer has become an escalating concern that necessitates vigilant surveillance. Nowadays, surgical intervention remains the optimal therapeutic approach for kidney cancer, while the availability of efficacious treatments for advanced tumors remains limited. Oncolytic viruses, an emerging form of immunotherapy, have demonstrated encouraging anti-neoplastic properties and are progressively garnering public acceptance. However, research on oncolytic viruses in kidney cancer is relatively limited. Furthermore, given the high complexity and heterogeneity of kidney cancer, it is crucial to identify an optimal oncolytic virus agent that is better suited for its treatment. The present study investigates the oncolytic activity of the Pseudorabies virus live attenuated vaccine (PRV-LAV) against KC. The findings clearly demonstrate that PRV-LAV exhibits robust oncolytic activity targeting KC cell lines. Furthermore, the therapeutic efficacy of PRV-LAV was confirmed in both a subcutaneous tumor-bearing nude mouse model and a syngeneic mouse model of KC. Combined RNA-seq analysis and flow cytometry revealed that PRV-LAV treatment substantially enhances the infiltration of a diverse range of lymphocytes, including T cells, B cells, macrophages, and NK cells. Additionally, PRV-LAV treatment enhances T cell activation and exerts antitumor effects. Importantly, the combination of PRV-LAV with anti-PD-1 antibodies, an approved drug for KC treatment, synergistically enhances the efficacy against KC. Overall, the discovery of PRV-LAV as an effective oncolytic virus holds significant importance for improving the treatment efficacy and survival rates of KC patients.
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Vacunas contra el Cáncer , Herpesvirus Suido 1 , Inhibidores de Puntos de Control Inmunológico , Neoplasias Renales , Virus Oncolíticos , Animales , Humanos , Ratones , Línea Celular Tumoral , Herpesvirus Suido 1/genética , Neoplasias Renales/terapia , Virus Oncolíticos/genética , Receptor de Muerte Celular Programada 1 , Microambiente Tumoral , Vacunas Atenuadas , Vacunas contra el Cáncer/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéuticoRESUMEN
A visible-light-induced radical alkylarylation of N-aryl bicyclobutyl amides with α-carbonyl alkyl bromides for the synthesis of functionalized 3-spirocyclobutyl oxindoles is described in which ß-selective radical addition of the alkyl radical to N-aryl bicyclobutyl amides forms a key radical intermediate followed by interception with intrinsic arene functional group. This approach can be applicable to a wide range of α-carbonyl alkyl bromides, including primary, secondary, and tertiary α-bromoalkyl esters, ketones, nitriles, and nitro compounds.
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BACKGROUND: This study aims to assess the influence of early serum phosphate fluctuation on the short-term prognosis of sepsis patients. METHODS: This retrospective study used the Medical Information Mart for Intensive Care IV database to analyze serum phosphate levels in sepsis patients within 3 days of ICU admission. According to the absolute value of delta serum phosphate (the maximum value minus the minimum value of serum phosphorus measured within three days), the patients were divided into four groups, 0-1.3, 1.4-2.0, 2.1-3.1, and ≥ 3.2 mg/dl. Meanwhile, the direction of delta serum phosphate was compared. With the serum phosphate change group of 0-1.3 mg/dl as the reference group, the relationship between delta serum phosphate and in-hospital mortality and 28-day mortality was analyzed by multivariate Logistics regression analysis. RESULTS: The study involved 1375 sepsis patients. Serum phosphate changes (0-1.3, 1.4-2.0, 2.1-3.1, and ≥ 3.2 mg/dl) correlated with in-hospital and 28-day mortality variations (p = 0.005, p = 0.008). Much higher serum phosphate fluctuation elevated in-hospital and 28-day mortality. Compared to the 0-1.3 mg/dl change group, adjusted odds ratios (OR) in other groups for in-hospital mortality were 1.25 (0.86-1.81), 1.28 (0.88-1.86), and 1.63 (1.10-2.43), and for 28-day mortality were 1.21 (0.86-1.72), 1.10 (0.77-1.57), and 1.49 (1.03-2.19). Under the trend of increasing serum phosphate, the ORs of in-hospital mortality and 28-day mortality in ≥ 3.2 mg/dl group were 2.52 and 2.01, respectively. CONCLUSION: In conclude, the delta serum phosphate ≥ 3.2 mg/dl was associated with in-hospital mortality and 28-day mortality in patients with sepsis.
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Unidades de Cuidados Intensivos , Sepsis , Humanos , Estudios Retrospectivos , Pronóstico , Hospitales , FosfatosRESUMEN
Thirty-six healthy 21-day-old weaned ternary piglets (Duroc × Landrace × Yorkshire) were randomly divided into two treatments with 18 replicates per treatment and one pig per replicate. The control group was fed with a basal diet and the test group was fed with diets supplemented with 1 kg/t tea residue. The test period was 28 days. The results are as follows: The addition of tea residue in the diet had no significant effect on the growth performance of weaned piglets (p > 0.05), but it could significantly reduce the diarrhea rate of piglets from 1 to 7 days and 1 to 28 days (p < 0.05). Compared with the control group, the dietary supplementation of tea residue had no significant effect on nutrient apparent digestibility, plasma biochemical indexes and plasma immune indexes (p > 0.05) but increased the content of glutathione in plasma (p < 0.05). Tea residue had no significant effect on the morphology of the jejunum and ileum of piglets (p > 0.05), but it could significantly reduce the content of chloride ions in feces (p < 0.05). Compared with the basal diet group, there was no significant difference in the relative expression of TMEM16A and CFTR mRNA in the colon of weaned piglets (p > 0.05). The whole-cell patch clamp recording showed that the TMEM16A and CFTR ion channels could be activated by ionomycin and forskolin, respectively. However, when HT-29 cells transfected with TMEM16A and CFTR channels were treated with tea residue extract, it could significantly inhibit the chloride current of the TMEM16A and CFTR ion channels (p < 0.05).
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A visible-light-induced radical cyclization reaction of o-vinylaryl isocyanides and oxime esters to access various 2,4-disubstituted quinolines was disclosed. Oxime esters were employed as acyl radical precursors via the carbon-carbon bond cleavage. It provided an effective way for the synthesis of 2-acyl-4-arlysubstituted quinolines under mild conditions and exhibited good functional group tolerance and substrate applicability.
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We herein report an efficient photoredox radical cyclization reaction of o-vinylaryl isocyanides with acyl chlorides to access a wide range of 2,4-disubstituted quinolines. Preliminary mechanism experiment results suggested that this reaction was initiated by an acyl radical generated from acyl chlorides through a single-electron-transfer (SET) process. This transformation showed good substrate suitability and functional group compatibility at room temperature.
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Objective: Gut microbiota is closely related to sepsis. Recent studies have suggested that Prevotellaceae could be associated with intestinal inflammation; however, the causal relationship between Prevotellaceae and sepsis remains uncertain. From the perspective of predictive, preventive, and personalized medicine (PPPM), exploring the causal relationship between gut Prevotellaceae and sepsis could provide opportunity for targeted prevention and personalized treatment. Methods: The genome-wide association study (GWAS) summary-level data of Prevotellaceae (N = 7738) and sepsis were obtained from the Dutch Microbiome Project and the UK Biobank (sepsis, 1380 cases; 429,985 controls). MR analysis was conducted to estimate the associations between Prevotellaceae and sepsis risk. The 16S rRNA sequencing analysis was conducted to calculate the relative abundance of Prevotellaceae in sepsis patients to explore the relationship between Prevotellaceae relative abundance and the 28-day mortality. Results: Genetic liability to f__Prevotellaceae (OR, 1.91; CI, 1.35-2.71; p = 0.0003) was associated with a high risk of sepsis with inverse-variance weighted (IVW). The median Prevotellaceae relative abundance in non-survivors was significantly higher than in survivors (2.34% vs 0.17%, p < 0.001). Multivariate analysis confirmed that Prevotellaceae relative abundance (OR, 1.10; CI, 1.03-1.22; p = 0.027) was an independent factor of 28-day mortality in sepsis patients. ROC curve analysis indicated that Prevotellaceae relative abundance (AUC: 0.787, 95% CI: 0.671-0.902, p = 0.0003) could predict the prognosis of sepsis patients. Conclusion: Our results revealed that Prevotellaceae was causally associated with sepsis and affected the prognosis of sepsis patients. These findings may provide insights to clinicians on developing improved sepsis PPPM strategies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00340-6.
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Cyclobutanone oximes and their derivatives are pivotal core structural motifs in organic chemistry. Iminyl-radical-triggered C-C bond cleavage of cyclobutanone oximes delivers an efficient strategy to produce stable distal cyano-substituted alkyl radicals, which can capture SO2, CO or O2 to form cyanoalkylsulfonyl radicals, cyanoalkylcarbonyl radicals or cyanoalkoxyl radicals under mild conditions. In the past several years, cyanoalkylsulfonylation/cyanoalkylcarbonyaltion/cyanoalkoxylation has attracted a lot of interest. In this updated report, the strategies for trapping SO2, CO or O2via iminyl-radical-triggered ring-opening of cyclobutanone oximes are summarized.