Alternation of gene expression in brain-derived exosomes after cerebral ischemic preconditioning in mice.

Aims: Cerebral ischemic preconditioning is a neuroprotective therapy against cerebral ischemia and ischemia-reperfusion injury. This study aims to demonstrate the alternation of gene expression in exosomes from brain tissue of mice after ischemic preconditioning and their potential functions. Methods: Ten mice were divided into the sham and the cerebral ischemic preconditioning groups. Their brain tissues were harvested, from which the exosomes were extracted. The characteristics and protective effects of exosomes were evaluated. Whole transcriptome sequencing was used to demonstrate the gene expression discrepancy between the exosomes from the two groups of mice brains. Volcano graphs and heatmaps were used to picture the difference in expression quantity of mRNA, lncRNA, and circRNA. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to demonstrate the functions of differentially expressed RNAs. Results: Exosomes were successfully extracted, and those from the cerebral ischemic preconditioning group had better protective effects on cells that received oxygen-glucose deprivation and restoration injury. A total of 306 mRNAs and 374 lncRNAs were significantly upregulated, and 320 mRNAs and 405 lncRNAs were significantly downregulated in the preconditioning group. No circRNAs were differentially expressed between the two groups. GO and KEGG pathway analysis indicated that the functions of differentially expressed RNAs were related to both neural protective and injurious effects. Conclusion: The brain-derived exosomes may participate in the neuroprotective effect of cerebral ischemic preconditioning. Thorough research is necessary to investigate exosome functions derived from the ischemic preconditioned brain.

Evaluation of greenhouse gas emission and reduction potential of high-food-waste-content municipal solid waste landfills: A case study of a landfill in the east of China.

This study proposes a comprehensive evaluation method based on a two-stage model to assess greenhouse gas (GHG) emissions and reductions in high-food-waste-content (HFWC) municipal solid waste (MSW) landfills. The proposed method considers typical processes such as fugitive landfill gas (LFG), LFG collection, flaring, power generation, and leachate treatment. A case study of an HFWC MSW landfill in eastern China is considered to illustrate the evaluation. The findings revealed that the GHG emissions equivalent of the case landfill amounted to 21.23 million tons from 2007 to 2022, averaging 1.03 tons CO2-eq per ton of MSW. There was a potential underestimation of LFG generation at the landfill site during the initial stages, which led to delayed LFG collection and substantial fugitive LFG emissions. Additionally, the time distribution of GHG emissions from HFWC MSW was significantly different from that of low-food-waste-content (LFWC) MSW landfills, with peak emissions occurring much earlier. Owing to the rapid degradation characteristics of HFWC MSW, the cumulative LFG production of the landfill by 2022 (2 years after the final cover) was projected to reach 77 % of the total LFG potential. In contrast, it would take until 2030 for LFWC MSW landfills to reach this level. Furthermore, various scenarios were analyzed, in which if the rapid LFG generation characteristics of HFWC MSW are known in advance, and relevant facilities are constructed ahead of time, the collection efficiency can be improved from 31 % to over 78 %, resulting in less GHG emissions.

Fabrication of food polysaccharide, protein, and polysaccharide-protein composite gels via calcium ion inducement: Gelation mechanisms, conditional factors, and applications.

Food gel is a kind of macromolecular biopolymer with viscoelasticity, which has good water retention and gelling ability, especially gels formed by protein and/or polysaccharide. The addition of calcium ions triggers gelation by interacting with the gel matrix, enhancing gels' textural and rheological properties like hardness, viscosity and elasticity. Thus calcium ions enrich the range of applications of food gels. This review focuses on forming a calcium-induced gel and improving the texture properties. It summarizes the mechanisms of gelation induced by calcium ions in polysaccharide, protein, and polysaccharide-protein systems and their gel properties. The effects of influencing factors in calcium ion concentration, types and mixing ratios of matrices, acid, and alkaline environments, as well as treatment methods on calcium-induced gel characteristics, are presented. Additionally, the current applications of calcium-induced gels in food industries and challenges are presented.

Using PRECIS-2 in Chinese herbal medicine randomized controlled trials for irritable bowel syndrome: A methodological exploration based on literature.

Background: The pragmatism levels of randomized controlled trials (RCTs) mean how similar the interventions delivered in the trial setting match those in the setting where the results will be applied. We aimed to investigate the association between the consistency of pragmatism among the characteristics of RCT design and its effect size of results in Chinese herbal medicine (CHM) for irritable bowel syndrome (IBS). Methods: Eight English and Chinese language databases were searched for RCTs on CHM for IBS. Six reviewers independently assessed the pragmatism of trials using the pragmatic-explanatory continuum indicator summary 2 (PRECIS-2) tool. The consistency of pragmatism levels among the characteristics of RCT design was calculated using the coefficient of variation. Linear regression models were adopted to explore influence factors of the pragmatism of RCTs. Results: 78 RCTs were included. The level of consistency in the pragmatism for RCT's design was significantly correlated with the effect size of the results (binary outcome, r = -0.413; P = 0.005; continuous outcome, r = -0.779, P < 0.001). PRECIS-2 score was higher in trials with individualized interventions than fixed interventions (3.29 [0.32] vs 2.90 [0.32]; Cohen's d relative effect size, 0.52; P < 0.001) and in standard or usual-treatment-controlled trials than placebo-controlled (3.05 [0.37] vs 2.83 [0.28]; Cohen's d relative effect size, 0.32; P = 0.048). Conclusion: The consistency of pragmatism level across the 9 domains of the PRECIS-2 tool in CHM IBS RCTs was positively correlated with the effect size of the results.

Integration of induction, system optimization and genetic transformation in Veratrum californicum var. vitro cultures to enhance the production of cyclopamine and veratramine.

Cyclopamine, a compound found in wild Veratrum has shown promising potential as a lead anti-cancer drug by effectively blocking cancer signaling pathways. However, its complex chemical structure poses challenges for artificial synthesis, thus limiting its supply and downstream drug production. This study comprehensively utilizes induction, system optimization, and transgenic technologies to establish an efficient suspension culture system for the high-yield production of cyclopamine and its precursor, veratramine. Experimental results demonstrate that methyl jasmonate (MeJA) effectively promotes the content of veratramine and cyclopamine in Veratrum californicum var. callus tissue, while yeast extract (YE) addition significantly increases cell biomass. The total content of veratramine and cyclopamine reached 0.0638 mg after synergistic treatment of suspension system with these two elicitors. And the content of the two substances was further increased to 0.0827 mg after the optimization by response surface methodology. Subsequently, a genetic transformation system for V. californicum callus was established and a crucial enzyme gene VnOSC1, involved in the steroidal alkaloid biosynthesis pathway, was screened and identified for genetic transformation. Combined suspension culture and synergistic induction system, the total content of the two substances in transgenic suspension system was further increased to 0.1228 mg, representing a 276.69% improvement compared to the initial culture system. This study proposes a complete and effective genetic transformation and cultivation scheme for V. californicum tissue cells, achieving milligram-level production of the anticancer agent cyclopamine and its direct precursor veratramine for the first time. It provides a theoretical basis for the industrial-scale production of these substances.

Fondaparinux Sodium for Anticoagulant Therapy After Primary Percutaneous Coronary Intervention: A Single-Center Randomized Trial in China.

ABSTRACT: In this study, we investigated the safety and efficacy of fondaparinux sodium in postpercutaneous coronary intervention (PCI) anticoagulation therapy for patients with ST-segment elevation myocardial infarction. There are a total of 200 patients with ST segment elevation myocardial infarction underwent PCI and anticoagulation therapy. They were randomly split into experimental (n = 108) and control groups (n = 92). The experimental group received postoperative fondaparinux sodium (2.5 mg q.d), while the control group received enoxaparin (4000 IU q12 h). We did not use a loading dose for enoxaparin. Bleeding incidence and major adverse cardiovascular/cerebrovascular events were monitored during hospitalization, and at 1, 3, and 6 months postsurgery. The primary end points, including bleeding, mortality, and myocardial infarction during hospitalization, were not significantly different between the 2 groups. For secondary end points, the incidence of combined end point events at 1 month, 3 months, and 6 months after surgery in the experimental group was lower than in the control group (P < 0.05). According to Cox regression analysis, the risk of bleeding in the experimental group was significantly lower than that in the control group [hazard ratios: 0.506, 95% confidence interval (CI): 0.284-0.900] (P = 0.020). The risk of mortality in the experimental group was significantly lower than in the control group (hazard ratio: 0.188, 95% CI: 0.040-0.889) (P = 0.035). In summary, perioperative use of fondaparinux sodium during PCI in patients with STEMI in this study was associated with a lower risk of bleeding and death compared with enoxaparin use in the absence of loading dose.

Efficacy and safety of first- and second-line antibiotics for cellulitis and erysipelas: a network meta-analysis of randomized controlled trials.

This study systematically evaluated and ranked the efficacy of first- and second-line antibiotics antibiotic options for the clinical management of cellulitis and erysipelas through a network meta-analysis approach. From inception to July 04, 2024, a search for relevant randomized clinical trials (RCTs) was carried out using several databases. Antibiotics including azithromycin, cefaclor, cephalexin, cloxacillin, erythromycin, cephalexin plus trimethoprim-sulfamethoxazole, cephalexin plus placebo, flucloxacillin, clindamycin, ceftriaxone, penicillin, roxithromycin, and pristinamycin were assessed regarding cure rate, the eradication of baseline pathogens, diarrhea or vomiting, and rash. In total, 10 RCTs with 1,936 cellulitis or erysipelas patients were eligible for inclusion. There were no significant differences in the cure rates for cellulitis among the antibiotics analysed, with cefaclor demonstrating the most favorable profile for curative outcomes. In terms of side effects, ceftriaxone was identified as the least likely to induce diarrhea or vomiting. For erysipelas, pristinamycin showed the most promising results in achieving cure rates. Although a comparison of the three antibiotics revealed no significant differences in rash as a side effect in erysipelas, pristinamycin was observed to carry the highest risk for rash. Our findings indicate no significant differences in cure rates among antibiotics for cellulitis. However, ceftriaxone had the fewest gastrointestinal side effects. Pristinamycin showed the highest cure rates for erysipelas but with a higher risk of rash. Future research should focus on optimizing antibiotic selection for cellulitis and erysipelas.

CYB561 is a potential therapeutic target for breast cancer and is associated with immune cell infiltration.

BACKGROUND: Breast cancer (BC), a common malignant tumor originating from the terminal ductal lobular unit of the breast, poses a substantial health risk to women. Previous studies have associated cytochrome b561 (CYB561) with a poor prognosis in BC; however, its underlying mechanism of this association remains unclear. METHODS: We investigated the expression of CYB561 mRNA in BC using databases such as The Cancer Genome Atlas, Gene Expression Omnibus, Tumor-Normal-Metastatic plot, and Kaplan-Meier plotter databases. The prognostic value of CYB561 protein in BC was assessed in relation to its expression levels in tumor tissue samples from 158 patients with BC. The effect of CYB561 on BC progression was confirmed using in vivo and in vitro experiments. The biological functions and related signaling pathways of CYB561 in BC were explored using gene microarray, Innovative Pathway, Gene Ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The correlation between CYB561 and the BC tumor immune microenvironment was evaluated using the CIBERSORT algorithm and single-cell analysis and further validated through immunohistochemistry of serial sections. RESULTS: Our study demonstrated that upregulation of CYB561 expression predicted poor prognosis in patients with BC and that CYB561 knockdown inhibited the proliferation, migration, and invasive ability of BC cells in vitro. CYB561 knockdown inhibited BC tumor formation in vivo.CYB561 was observed to modulate downstream tropomyosin 1 expression. Furthermore, CYB561 expression was associated with macrophage M2 polarization in the BC immune microenvironment. CONCLUSIONS: Elevated CYB561 expression suggests a poor prognosis for patients with BC and is associated with macrophage M2 polarization in the BC microenvironment. Therefore, CYB561 could potentially serve as a therapeutic target for BC treatment.

Versatility of the supraclavicular artery island flap for head and neck reconstruction.

Objective: To present our experience using the supraclavicular artery island flap (SCAIF) for head and neck reconstruction. Methods: We performed a retrospective chart review to identify patients who underwent head and neck reconstruction with SCAIF at our institution. The following data were collected: age, sex, surgical indications, flap harvest time, flap dimensions, length of hospital stay, complications, and clinical outcomes. Results: Thirty-three patients underwent SCAIF reconstruction, of whom four underwent pectoralis major myocutaneous flap reconstruction simultaneously. Twenty flaps were used to repair pharyngeal or esophageal defects following resection for tonsillar, hypopharyngeal, laryngeal, and cervical esophageal cancers. Five flaps were used for tracheal reconstruction following resection for tracheal or thyroid gland cancer. Seven flaps were used for reconstruction of cervical skin defects or fistulas related to a previous treatment. One flap for tracheal stenosis following tracheotomy. The mean age of the patients was 60.69 ± 11.47 years. The mean flap harvest time was 32.00 ± 4.44 min. The mean flap size was 10.16 ± 3.91 × 5.78 ± 0.68 cm. The mean length of hospital stay is 24.84 ± 13.78 days. Three patients had partial necrosis of the distal portion of the flap, which resolved with anti-infection therapy and local wound care. One patient developed a fistula that was resolved with wound care and further surgical intervention. Complete flap loss or major complications were not observed. No donor site complication or compromised shoulder function was observed. Conclusion: The SCAIF can be successfully used to reconstruct head and neck defects with good outcomes and limited morbidity. Level of Evidence: 4.

Structure-Activity Relationships and Changes in the Inhibition of Xanthine Oxidase by Polyphenols: A Review.

Hyperuricemia (HUA), or elevated uric acid in the blood, has become more prevalent in recent years. Polyphenols, which are known to have good inhibitory activity on xanthine oxidoreductase (XOR), are effective in uric acid reduction. In this review, we address the structure-activity relationship of flavonoids that inhibit XOR activity from two perspectives: the key residues of XOR and the structural properties of flavonoids. Flavonoids' inhibitory effect is enhanced by their hydroxyl, methoxy, and planar structures, whereas glycosylation dramatically reduces their activity. The flavonoid structure-activity relationship informed subsequent discussions of the changes that occur in polyphenols' XOR inhibitory activity during their extraction, processing, gastrointestinal digestion, absorption, and interactions. Furthermore, gastrointestinal digestion and heat treatment during processing can boost the inhibition of XOR. Polyphenols with comparable structures may have a synergistic effect, and their synergy with allopurinol thus provides a promising future research direction.

Characterization and application of Bacillus velezensis D6 co-producing α-amylase and protease.

BACKGROUND: Research on the co-production of multiple enzymes by Bacillus velezensis as a novel species is still a topic that needs to be studied. This study aimed to investigate the fermentation characteristics of B. velezensis D6 co-producing α-amylase and protease and to explore their enzymatic properties and applications in fermentation. RESULTS: The maximum co-production of α-amylase and protease reached 13.13 ± 0.72 and 2106.63 ± 64.42 U mL-1, respectively, under the optimal fermented conditions (nutrients: 20.0 g L-1 urea, 20.0 g L-1 glucose, 0.7 g L-1 MnCl2; incubation conditions: initial pH 7.0, temperature 41 °C, 8% inoculation size and 30% working volume). Moreover, the genetic co-expression of α-amylase and protease increased from 0 to 24 h and then decreased after 36 h at the transcriptional level, which coincided with the growth trend of B. velezensis D6. The optimal reaction temperature of α-amylase was 55-60 °C, while that of protease was 35-40 °C. The activities of α-amylase and protease were retained by over 80% after thermal treatment (90 °C, 1 h), which indicated that two enzymes co-produced by B. velezensis D6 demonstrated excellent thermal stability. Moreover, the two enzymes were stable over a wide pH range (pH 4.0-8.0 for α-amylase; pH 4.0-9.0 for protease). Finally, the degrees of hydrolysis of corn, rice, sorghum and soybeans by α-amylase from B. velezensis D6 reached 44.95 ± 2.95%, 57.16 ± 2.75%, 52.53 ± 4.01% and 20.53 ± 2.42%, respectively, suggesting an excellent hydrolysis effect on starchy raw materials. The hydrolysis degrees of mackerel heads and soybeans by protease were 43.93 ± 2.19% and 26.38 ± 1.72%, respectively, which suggested that the protease from B. velezensis D6 preferentially hydrolyzed animal-based protein. CONCLUSION: This is a systematic study on the co-production of α-amylase and protease by B. velezensis D6, which is crucial in widening the understanding of this species co-producing multi-enzymes and in exploring its potential application. © 2024 Society of Chemical Industry.

Animal Models of Helicobacter pylori Infection and Vaccines: Current Status and Future Prospects.

Helicobacter pylori infection causes chronic gastritis, ulcers, and gastric cancer, making it a threat to human health. Despite the use of antibiotic therapy, the global prevalence of H. pylori infection remains high, necessitating early eradication measures. Immunotherapy, especially vaccine development, is a promising solution in this direction, albeit the selection of an appropriate animal model is critical in efficient vaccine production. Accordingly, we conducted a literature, search and summarized the commonly used H. pylori strains, H. pylori infection-related animal models, and models for evaluating H. pylori vaccines. Based on factors such as the ability to replicate human diseases, strain compatibility, vaccine types, and eliciting of immune responses, we systematically compared the advantages and disadvantages of different animal models, to obtain the informed recommendations. In addition, we have proposed novel perspectives on H. pylori-related animal models to advance research and vaccine evaluation for the prevention and treatment of diseases such as gastric cancer.

Large-scale genetic correlation studies explore the causal relationship and potential mechanism between gut microbiota and COVID-19-associated risks.

Recent observational studies suggest that gut microorganisms are involved in the onset and development of coronavirus disease 2019 (COVID-19), but the potential causal relationship behind them remains unclear. Exposure data were derived from the MiBioGen consortium, encompassing 211 gut microbiota (n = 18,340). The outcome data were sourced from the COVID-19 host genetics initiative (round 7), including COVID-19 severity (n = 1,086,211), hospitalization (n = 2,095,324), and susceptibility (n = 2,597,856). First, a two-sample Mendelian randomization (TSMR) was performed to investigate the causal effect between gut microbiota and COVID-19 outcomes. Second, a two-step MR was used to explore the potential mediators and underlying mechanisms. Third, several sensitivity analyses were performed to verify the robustness of the results. Five gut microbes were found to have a potential causality with COVID-19 severity, namely Betaproteobacteria (beta = 0.096, p = 0.034), Christensenellaceae (beta = -0.092, p = 0.023), Adlercreutzia (beta = 0.072, p = 0.048), Coprococcus 1 (beta = 0.089, p = 0.032), Eisenbergiella (beta = 0.064, p = 0.024). Seven gut microbes were found to have a potential causality with COVID-19 hospitalization, namely Victivallaceae (beta = 0.037, p = 0.028), Actinomyces (beta = 0.047, p = 0.046), Coprococcus 2 (beta = -0.061, p = 0.031), Dorea (beta = 0.067, p = 0.016), Peptococcus (beta = -0.035, p = 0.049), Rikenellaceae RC9 gut group (beta = 0.034, p = 0.018), and Proteobacteria (beta = -0.069, p = 0.035). Two gut microbes were found to have a potential causality with COVID-19 susceptibility, namely Holdemanella (beta = -0.024, p = 0.023) and Lachnospiraceae FCS020 group (beta = 0.026, p = 0.027). Multi-omics mediation analyses indicate that numerous plasma proteins, metabolites, and immune factors are critical mediators linking gut microbiota with COVID-19 outcomes. Sensitivity analysis suggested no significant heterogeneity or pleiotropy. These findings revealed the causal correlation and potential mechanism between gut microbiota and COVID-19 outcomes, which may improve our understanding of the gut-lung axis in the etiology and pathology of COVID-19 in the future.

Metabolic engineering of artificially modified transcription factor SmMYB36-VP16 for high-level production of tanshinone and phenolic acids.

Tanshinone and phenolic acids are the two main chemical constituents in Salvia miltiorrhiza, which are used clinically for the treatment of hypertension, coronary heart disease, atherosclerosis, and many other diseases, and have broad medicinal value. The efficient synthesis of the target products of these two metabolites in isolated plant tissues cannot be achieved without the regulation and optimization of metabolic pathways, and transcription factors play an important role as common regulatory elements in plant tissue metabolic engineering. However, most of the regulatory effects are specific to one class of metabolites, or an opposing regulation of two classes of metabolites exists. In this study, an artificially modified transcription factor, SmMYB36-VP16, was constructed to enhance tanshinone and phenolic acids in Salvia miltiorrhiza hair roots simultaneously. Further in combination with the elicitor dual-screening technique, by applying the optimal elicitors screened, the tanshinone content in the transgenic hairy roots of Salvia miltiorrhiza reached 6.44 mg/g DW, which was theoretically 6.08-fold that of the controls without any treatment, and the content of phenolic acids reached 141.03 mg/g DW, which was theoretically 5.05-fold that of the controls without any treatment. The combination of artificially modified transcriptional regulatory and elicitors dual-screening techniques has facilitated the ability of plant isolated tissue cell factories to produce targeted medicinal metabolites. This strategy could be applied to other species, laying the foundation for the production of potential natural products for the medicinal industry.

Drug delivery under cover of erythrocytes extends drug half-life: A thrombolytic targeting therapy utilizing microenvironment-responsive artificial polysaccharide microvesicles.

The development of thrombolytic drug carriers capable of thrombus-targeting, prolonged circulation time, intelligent responsive release, and the ability to inhibit thrombotic recurrences remains a promising but significant challenge. To tackle this, an artificial polysaccharide microvesicle drug delivery system (uPA-CS/HS@RGD-ODE) was constructed. It is composed of cationic chitosan and anionic heparin assembled in a layer by layer structure, followed by surface modification using RGD peptide and 2-(N-oxide-N,N-diethylamino) ethylmethacrylate (ODE) before encapsulation of urokinase-type plasminogen activator (uPA). The effect of chitosan on the basic performances of uPA-CS/HS@RGD-ODE was estimated. The in vitro results suggest the uPA carrier, CS/HS@RGD-ODE, displayed outstanding targeting specific to activated platelets (61 %) and microenvironment-responsiveness at pH 6.5, facilitating thrombus-targeting and a controlled drug release, respectively. Most importantly, in vivo experiment suggests ODE from uPA-CS/HS@RGD-ODE substantially extends the half-life of uPA (120 min), as uPA-CS/HS@RGD-ODE can adhere onto erythrocytes and deliver uPA under cover of erythrocytes enabling a prolonged circulation time in the bloodstream. Further tail vein and abdominal aorta thrombosis models confirmed uPA-CS/HS@RGD-ODE exhibited superior targeting and thrombolysis capabilities compared to systemic administration of free uPA. To the knowledge of authors, this may be the first study to develop new drug carriers for delivery of thrombolytic drugs under the cover of erythrocytes for extended drug half-lives.

Analysis of assisted reproductive outcomes for gynecologic cancer survivors: a retrospective study.

OBJECTIVE: To examine the reproductive outcomes of assisted reproductive technology (ART) in gynecologic cancer patients and to assess maternal and neonatal complications. METHODS: Women diagnosed with gynecologic cancer who underwent their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment between 2013 and 2021 at Shanghai Ji Ai Genetics and IVF Institute were included in this study. Infertile women without any history of cancer were matched to the cancer group. The primary outcome was the cumulative live birth rate. Baseline and follow-up data were compared between groups using Student's t-tests for normally distributed variables and with Chi-square test for categorical variables. A propensity score-based patient-matching approach was adopted to ensure comparability between individuals with and without specific cancer type. RESULTS: A total of 136 patients with a history of gynecologic cancer and 241 healthy infertile controls were included in this study. Endometrial cancer constituted 50.70% of the cases and cervical cancer constituted 34.60% of the cases. The cancer group exhibited significantly shorter duration of stimulation, lower levels of estradiol, lower number of retrieved oocytes, day-3 embryos, and blastocysts compared to the control group (P < 0.05). The cumulative live birth rate of the gynecologic cancer group was significantly lower than that of the control group (36.10% vs. 60.50%, P < 0.001). Maternal and neonatal complications did not significantly differ between the groups (P > 0.05). The endometrial cancer and cervical cancer groups showed significantly lower cumulative live birth rates than their matched controls (38.60% vs. 64.50%, P = 0.011 and 24.20% vs. 68.60%, P < 0.001, respectively). CONCLUSIONS: These findings highlight the decreased occurrence of pregnancy and live birth in female gynecologic cancer patients undergoing ART, particularly in endometrial cancers and cervical cancers. These findings have important implications for counseling and managing gynecologic cancer patients undergoing ART.

Enhanced Electrochemical Sensing of Oxalic Acid Based on VS2 Nanoflower-Decorated Glassy Carbon Electrode Prepared by Hydrothermal Method.

Oxalic acid (OA) is a predominant constituent in kidney stones, contributing to 70-80% of all cases. Rapid detection of OA is vital for the early diagnosis and treatment of kidney stone conditions. This work introduces a novel electrochemical sensing approach for OA, leveraging vanadium disulfide (VS2) nanoflowers synthesized via hydrothermal synthesis. These VS2 nanoflowers, known for their excellent electrocatalytic properties and large surface area, are used to modify glassy carbon electrodes for enhanced OA sensing. The proposed OA sensor exhibits high sensitivity and selectivity across a wide linear detection range of 0.2-20 µM, with an impressively low detection limit of 0.188 µM. The practicality of this sensor was validated through interference studies, offering a promising tool for the early diagnosis and monitoring of kidney stone diseases.

Correction: Liu et al. Tamarixia radiata Behaviour Is Influenced by Volatiles from Both Plants and Diaphorina citri Nymphs. Insects 2019, 10, 141.

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A novel combined nomogram for predicting severe acute lower respiratory tract infection in children hospitalized for RSV infection during the post-COVID-19 period.

Introduction: Off-season upsurge of respiratory syncytial virus (RSV) infection with changed characteristics and heightened clinical severity during the post-COVID-19 era are raising serious concerns. This study aimed to develop and validate a nomogram for predicting the risk of severe acute lower respiratory tract infection (SALRTI) in children hospitalized for RSV infection during the post-COVID-19 era using machine learning techniques. Methods: A multicenter retrospective study was performed in nine tertiary hospitals in Yunnan, China, enrolling children hospitalized for RSV infection at seven of the nine participating hospitals during January-December 2023 into the development dataset. Thirty-nine variables covering demographic, clinical, and laboratory characteristics were collected. Primary screening and dimension reduction of data were performed using Least Absolute Shrinkage and Selection Operator (LASSO) regression, followed by identification of independent risk factors for RSV-associated SALRTI using Logistic regression, thus finally establishing a predictive nomogram model. Performance of the nomogram was internally evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) based on the development dataset. External validation of our model was conducted using same methods based on two independent RSV cohorts comprising pediatric RSV inpatients from another two participating hospitals between January-March 2024. Results: The development dataset included 1102 patients, 239 (21.7%) of whom developed SALRTI; while the external validation dataset included 249 patients (142 in Lincang subset and 107 in Dali subset), 58 (23.3%) of whom were diagnosed as SALRTI. Nine variables, including age, preterm birth, underlying condition, seizures, neutrophil-lymphocyte ratio (NLR), interleukin-6 (IL-6), lactate dehydrogenase (LDH), D-dimer, and co-infection, were eventually confirmed as the independent risk factors of RSV-associated SALRTI. A predictive nomogram was established via integrating these nine predictors. In both internal and external validations, ROC curves indicated that the nomogram had satisfactory discrimination ability, calibration curves demonstrated good agreement between the nomogram-predicted and observed probabilities of outcome, and DCA showed that the nomogram possessed favorable clinical application potential. Conclusion: A novel nomogram combining several common clinical and inflammatory indicators was successfully developed to predict RSV-associated SALRTI. Good performance and clinical effectiveness of this model were confirmed by internal and external validations.

COPZ1 regulates ferroptosis through NCOA4-mediated ferritinophagy in lung adenocarcinoma.

BACKGROUND: Ferroptosis, a type of autophagy-dependent cell death, has been implicated in the pathogenesis of lung adenocarcinoma (LUAD). This study aimed to investigate the involvement of coatomer protein complex I subunit zeta 1 (COPZ1) in ferroptosis and ferritinophagy in LUAD. METHODS: Publicly available human LUAD sample data were obtained from the TCGA database to analyze the association of COPZ1 expression with LUAD grade and patient survival. Clinical samples of LUAD and para-carcinoma tissues were collected. COPZ1-deficient LUAD cell model and xenograft model were established. These models were analyzed to evaluate tumor growth, lipid peroxidation levels, mitochondrial structure, autophagy activation, and iron metabolism. RESULTS: High expression of COPZ1 was indicative of malignancy and poor overall survival. Clinical LUAD tissues showed increased COPZ1 expression and decreased nuclear receptor coactivator 4 (NCOA4) expression. COPZ1 knockdown inhibited xenograft tumor growth and induced apoptosis. COPZ1 knockdown elevated the levels of ROS, Fe2+ and lipid peroxidation. COPZ1 knockdown also caused mitochondrial shrinkage. Liproxstatin-1, deferoxamine, and z-VAD-FMK reversed the effects of COPZ1 knockdown on LUAD cell proliferation and ferroptosis. Furthermore, COPZ1 was directly bound to NCOA4. COPZ1 knockdown restricted FTH1 expression and promoted NCOA4 and LC3 expression. NCOA4 knockdown reversed the regulation of iron metabolism, lipid peroxidation, and mitochondrial structure induced by COPZ1 knockdown. COPZ1 knockdown induced the translocation of ferritin to lysosomes for degradation, whereas NCOA4 knockdown disrupted this process. CONCLUSION: This study provides novel evidence that COPZ1 regulates NCOA4-mediated ferritinophagy and ferroptosis. These findings provide new insights into the pathogenesis and potential treatment of LUAD.