Efficacy of nab­paclitaxel vs. Gemcitabine in combination with S­1 for advanced pancreatic cancer: A multicenter phase II randomized trial.

Patients with advanced pancreatic cancer (PC) need a cost-effective treatment regimen. The present study was designed to compare the efficacy and safety of nab-paclitaxel plus S-1 (AS) and gemcitabine plus S-1 (GS) regimens in patients with chemotherapy-naïve advanced PC. In this open-label, multicenter, randomized study named AvGmPC, eligible patients with chemotherapy-naïve advanced PC were randomly assigned (1:1) to receive AS (125 mg/m2 nab-paclitaxel, days 1 and 8; 80-120 mg S-1, days 1-14) or GS (1,000 mg/m2 gemcitabine, days 1 and 8; 80-120 mg S-1, days 1-14). The treatment was administered every 3 weeks until intolerable toxicity or disease progression occurred. The primary endpoint was progression-free survival (PFS). Between December 2018 and March 2022, 101 of 106 randomized patients were treated and evaluated for analysis (AS, n=49; GS, n=52). As of the data cutoff, the median follow-up time was 11.37 months [95% confidence interval (CI), 9.31-13.24]. The median PFS was 7.16 months (95% CI, 5.19-12.32) for patients treated with AS and 6.41 months (95% CI, 3.72-8.84) for patients treated with GS (HR=0.78; 95% CI, 0.51-1.21; P=0.264). The AS regimen showed a slightly improved overall survival (OS; 13.27 vs. 10.64 months) and a significantly improved ORR (44.90 vs. 15.38%; P=0.001) compared with the GS regimen. In the subgroup analyses, PFS and OS benefits were observed in patients treated with the AS regimen who had KRAS gene mutations and high C-reactive protein (CRP) levels (≥5 mg/l). The most common grade ≥3 adverse events were neutropenia, anemia and alopecia in the two groups. Thrombocytopenia occurred more frequently in the GS group than in the AS group. While the study did not meet the primary endpoint, the response benefit observed for AS may be suggestive of meaningful clinical activity in this population. In particular, promising survival benefits were observed in the subsets of patients with KRAS gene mutations and high CRP levels, which is encouraging and warrants further investigation. This trial was retrospectively registered as ChiCTR1900024588 on July 18, 2019.

Altering optical zone diameter, reverse curve width, and compression factor: impacts on visual performance and axial elongation in orthokeratology.

PURPOSE: To investigate the effects of modifications in back optical zone diameter (BOZD), reverse curve width (RCW), and compression factor (CF) on refractive error changes and axial elongation in myopic children undergoing orthokeratology (ortho-k) over a 12-month period. METHOD: In this retrospective study, data from 126 myopic children undergoing ortho-k fitting were analyzed. Subjects were categorized into four distinct groups based on lens design parameters: Group A (BOZD 6.0 mm, RCW 0.6 mm, CF 0.75 D); Group B (BOZD 6.0 mm, RCW 0.6 mm, CF 1.25 D); Group C (BOZD 5.4 mm, RCW 0.9 mm, CF 1.25 D); and Group D (BOZD 5.0 mm, RCW 1.1 mm, CF 1.25 D). The study evaluated uncorrected visual acuity (UCVA), corneal topography, and axial length (AL) at intervals, using Linear Mixed Models (LMMs) for time-based changes, and ANOVA or Kruskal-Wallis tests for group differences in AL elongation. A multivariable regression analysis identified factors independently associated with AL elongation. RESULTS: Within the first day and week, all four groups displayed significant improvements in UCVA and alterations in corneal curvature, which subsequently stabilized. Although UCVA variations between groups were subtle, Group D had less corneal curvature change than Groups A and B initially and exhibited significantly less AL elongation after one year. No significant difference in corneal curvature change or AL elongation was observed between Group C and the other groups. Multiple regression analysis indicated that older baseline age, greater baseline spherical equivalent refractive error, and smaller BOZD were associated with less AL elongation. CONCLUSION: The study reveals a positive correlation between BOZD and axial length growth over the 12-month period. A pure 0.5 D CF increment demonstrates a nonsignificant impact. This study provides new ideas into optimizing the parameters of ortho-k lenses.

A novel lysosome-related prognostic signature associated with prognosis and immune infiltration landscape in oral squamous cell carcinoma.

Background: Predicting the outcome of oral squamous cell carcinoma (OSCC) is challenging due to its diverse nature and intricate causes. This research explores how lysosome-associated genes (LRGs) might forecast overall survival (OS) and correlate with immune infiltration in OSCC patients. Methods: We analyzed OSCC patients' LRGs' mRNA expression data and clinical details from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Through univariate Cox regression, we pinpointed LRGs with prognostic potential. A signature comprising 12 LRGs linked to prognosis was developed via the Least Absolute Shrinkage and Selection Operator (LASSO) in a training dataset. Patients were classified as higher or lower risk based on their risk scores, and the prognostic independence of the risk score was assessed using multivariate analysis. The model's robustness and precision were confirmed through bioinformatics in the GEO test set. Differential gene expression analysis between risk groups highlighted functional disparities, while various immune evaluation methods elucidated immune differences. Results: The prognostic framework utilized 12 LRGs (SLC46A3, MANBA, NEU1, SDCBP, BRI3, TMEM175, CD164, GPC1, SFTPB, TPP1, Biglycan (BGN) and TMEM192), showing that higher risk was associated with poorer OS. This set of genes independently predicted OS in OSCC, linking LRGs to cellular adhesion and extracellular matrix involvement. Initial assessments using ssGSEA and CIBERSORT suggested that the adverse outcomes in the higher-risk cohort may be tied to immune system deregulation. Conclusion: Twelve-LRGs signature has been identified for OSCC prognosis prediction, offering novel directions for lysosome-targeted therapies against OSCC.

Single-cell RNA sequencing reveals roles of unique retinal microglia types in early diabetic retinopathy.

BACKGROUND: The pathophysiological mechanisms of diabetic retinopathy (DR), a blinding disease, are intricate. DR was thought to be a microvascular disease previously. However, growing studies have indicated that the retinal microglia-induced inflammation precedes microangiopathy. The binary concept of microglial M1/M2 polarization paradigms during inflammatory activation has been debated. In this study, we confirmed microglia had the most significant changes in early DR using single-cell RNA sequencing. METHODS: A total of five retinal specimens were collected from donor SD rats. Changes in various cells of the retina at the early stage of DR were analyzed using single-cell sequencing technology. RESULTS: We defined three new microglial subtypes at cellular level, including two M1 types (Egr2+ M1 and Egr2- M1) and one M2 type. We also revealed the anatomical location between these subtypes, the dynamic changes of polarization phenotypes, and the possible activation sequence and mutual activation regulatory mechanism of different cells. Furthermore, we constructed an inflammatory network involving microglia, blood-derived macrophages and other retinal nonneuronal cells. The targeted study of new disease-specific microglial subtypes can shorten the time for drug screening and clinical application, which provided insight for the early control and reversal of DR. CONCLUSIONS: We found that microglia show the most obvious differential expression changes in early DR and reveal the changes in microglia in a high-glucose microenvironment at the single-cell level. Our comprehensive analysis will help achieve early reversal and control the occurrence and progression of DR.

Prediction of global wheat cultivation distribution under climate change and socioeconomic development.

Socioeconomic and climate change are both essential factors affecting the global cultivation distributions of crops. However, the role of socioeconomic factors in the prediction of future crop cultivation distribution under climate change has been rarely explored. Motivated by revealing the future global wheat cultivation distribution that coupling socioeconomic factors and climate change, the MaxEnt-SPAM approach was proposed by the present study. Furthermore, the spatial and temporal patterns of global wheat cultivation in the near-term (2011-2040), the mid-term (2041-2070), and long-term (2071-2100) under the scenarios of RCP2.6-SSP1, RCP4.5-SSP2, and RCP8.5-SSP3 were predicted. It indicated that the predictive accuracy of the proposed approach could be over 80 %, with a significant positive correlation (p < 0.01) between the predicted global wheat cultivation and multiple known datasets. Socioeconomic development significantly altered the potential distribution of global wheat cultivation driven by climate change. Socioeconomic development seems to benefit wheat cultivation in the Southern Hemisphere especially central and east Africa, while the Northern Hemisphere may have witnessed a decline in future cultivation areas. It was noteworthy that heightened profitability stimulated interest in expanding wheat cultivation efforts within pivotal countries/regions positioned in the Southern Hemisphere. In the long-term period, the potential wheat cultivation area was reduced by 7 % under the RCP2.6-SSP1 scenario, while it expanded by 8 % and 2 % under the RCP4.5-SSP2 and RCP8.5-SSP3 scenarios, respectively. A global decline in wheat production of 16 %, 3 %, and 3 % was observed in the long-term under the RCP2.6-SSP1, RCP4.5-SSP2, and RCP8.5-SSP3 scenarios respectively. The present study emphasized the importance of integrating socioeconomic factors into crop distribution predictions under climate change. Our findings indicated significant temporal adjustments in the future global distribution of wheat cultivation and offered a comprehensive perspective on how socioeconomic factors interacted with climate change to influence global wheat cultivation.

Recent Advances in the Therapeutic Potential of Sinomenine for Cancer Treatment.

BACKGROUND: Cancer is a major cause of death worldwide. Although modern medicine has made strides in treatment, a complete cure for cancer remains elusive. SUMMARY: Utilization of medicinal plants in traditional medicine for the treatment of multiple diseases, including cancer, is a well-established practice. Sinomenine is an alkaloid extracted from a medicinal plant and has a diverse range of biological properties, including anti-oxidative, anti-inflammatory, and antibacterial effects. Sinomenine exhibits inhibitory effects on various types of tumor cells, including breast, lung, and liver cancers. The anticancer properties of sinomenine are believed to involve stimulation of apoptosis and autophagy as well as suppression of cell proliferation, invasion, and metastasis. KEY MESSAGE: This review summarizes the current research on sinomenine's potential as an anticancer agent, which may contribute to the discovery of more effective cancer treatments.

Safety, immunogenicity, and efficacy of a modified COVID-19 mRNA vaccine, SW-BIC-213, in healthy people aged 18 years and above: a phase 3 double-blinded, randomized, parallel controlled clinical trial in Lao PDR (Laos).

Background: The mRNA vaccine has demonstrated significant effectiveness in protecting against SARS-CoV-2 during the pandemic, including against severe forms of the disease caused by emerging variants. In this study, we examined safety, immunogenicity, and relative efficacy of a heterologous booster of the lipopolyplex (LPP)-based mRNA vaccine (SW-BIC-213) versus a homologous booster of an inactivated vaccine (BBIBP) in Laos. Methods: In this phase 3 clinical trial, which was randomized, parallel controlled and double-blinded, healthy adults aged 18 years and above were recruited from the Southern Savannakhet Provincial Hospital and Champhone District Hospital. The primary outcomes were safety and immunogenicity, with efficacy as an exploratory endpoint. Participants who were fully immunized with a two-dose inactivated vaccine for more than 6 months were assigned equally to either the SW-BIC-213 group (25 µg) or BBIBP group. The primary safety endpoint was to describe the safety profile of all participants in each group up to 6 months post-booster immunization. The primary immunogenic outcome was to demonstrate the superiority of the neutralizing antibody response, in terms of geometric mean titers (GMTs) of SW-BIC-213, compared with BBIBP 28 days after the booster dose. The exploratory efficacy endpoint aimed to assess the relative efficacy of SW-BIC-213 compared to BBIBP against virologically confirmed symptomatic COVID-19 over a 6-month period. The trial was registered with ClinicalTrials.gov (NCT05580159). Findings: Between October 10, 2022, and January 13, 2023, 1200 participants were assigned to SW-BIC-213 group and 1203 participants in the BBIBP group. All adverse reactions observed during the study were tolerable, transient, and resolved spontaneously. Solicited local reactions were the main adverse reactions in both the SW-BIC-213 group (43.8%) and BBIBP group (14.8%) (p < 0.001). Heterologous boosting with SW-BIC-213 induced higher live virus neutralizing antibodies to SARS-CoV-2 wildtype and BA.5 strains with GMTs reaching 750.1 and 192.9 than homologous boosting with BBIBP with GMTs of 131.5 (p < 0.001) and 47.5 (p < 0.001) on day 29. The statistical findings revealed that, following a period of 14-day to 6-month after booster vaccination, the SW-BIC-213 group exhibited a relative vaccine efficacy (VE) of 70.1% (95% CI: 34.2-86.4) against symptomatic COVID-19 when compared to the BBIBP group. Interpretation: A heterologous booster with the COVID-19 mRNA vaccine SW-BIC-213 manifests a favorable safety profile and proves highly immunogenic and efficacious in preventing symptomatic COVID-19 in individuals who have previously received two doses of inactivated vaccine. Funding: Shanghai Strategic Emerging Industries Development Special Fund, Biomedical Technology Support Special Project of Shanghai "Science and Technology Innovation Action Plan", Shanghai Municipal Science and Technology Commission.

Effect of homeostatic pressure and circadian rhythm on the task-switching: Evidence from drift diffusion model and ERP.

The effect of diurnal fluctuations on cognitive functions is widely studied, yet rare research has attempted to separate the role of two crucial processes underlying diurnal fluctuations: homeostatic pressure and circadian rhythm. The present study aimed to dissociate their effects by conducting a task-switching task in the morning, napping afternoon, and no-napping afternoon, respectively. Additionally, DDM and ERP were utilized to explore how these two processes differentially affect cognitive processes involved in task-switching. By a within-participant design, 35 healthy adults (20.03 ± 2.01 year-old, 14 males) with an intermediate-type chronotype were recruited in the current study. The results demonstrated that accumulated homeostatic pressure caused reduced accuracy, drift rate, and decision threshold. In the no-napping afternoon, P1 and P2 amplitudes were also decreased due to homeostatic pressure, whereas an afternoon nap could partially restore performance and neural activity. Conversely, the upward circadian rhythm in the afternoon exerted a compensatory effect, resulting in increases in N2 and P3 amplitudes. The findings highlight the disassociated impacts of homeostatic pressure and circadian rhythm on the cognitive processes involved in task-switching and further underscore the importance of considering diurnal variation in both scientific research and accident prevention.

Zebrafish spop promotes ubiquitination and degradation of mavs to suppress antiviral response via the lysosomal pathway.

Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) signaling pathways are required to be tightly controlled to initiate host innate immune responses. Fish mitochondrial antiviral signaling (mavs) is a key determinant in the RLR pathway, and its ubiquitination is associated with mavs activation. Here, we identified the zebrafish E3 ubiquitin ligase Speckle-type BTB-POZ protein (spop) negatively regulates mavs-mediated the type I interferon (IFN) responses. Consistently, overexpression of zebrafish spop repressed the activity of IFN promoter and reduced host ifn transcription, whereas knockdown spop by small interfering RNA (siRNA) transfection had the opposite effects. Accordingly, overexpression of spop dampened the cellular antiviral responses triggered by spring viremia of carp virus (SVCV). A functional domain assay revealed that the N-terminal substrate-binding MATH domain regions of spop were necessary for IFN suppression. Further assays indicated that spop interacts with mavs through the C-terminal transmembrane (TM) domain of mavs. Moreover, zebrafish spop selectively promotes K48-linked polyubiquitination and degradation of mavs through the lysosomal pathway to suppress IFN expression. Our findings unearth a post-translational mechanism by which mavs is regulated and reveal a role for spop in inhibiting antiviral innate responses.

Increased Expression of KNa1.2 Channel by MAPK Pathway Regulates Neuronal Activity Following Traumatic Brain Injury.

Recent studies have indicated that functional abnormalities in the KNa1.2 channel are linked to epileptic encephalopathies. However, the role of KNa1.2 channel in traumatic brain injury (TBI) remains limited. We collected brain tissue from the TBI mice and patients with post-traumatic epilepsy (PTE) to determine changes in KNa1.2 channel following TBI. We also investigated whether the MAPK pathway, which was activated by the released cytokines after injury, regulated KNa1.2 channel in in vitro. Finally, to elucidate the physiological significance of KNa1.2 channel in neuronal excitability, we utilized the null mutant-Kcnt2-/- mice and compared their behavior patterns, seizure susceptibility, and neuronal firing properties to wild type (WT) mice. TBI was induced in both Kcnt2-/- and WT mice to investigate any differences between the two groups under pathological condition. Our findings revealed that the expression of KNa1.2 channel was notably increased only during the acute phase following TBI, while no significant elevation was observed during the late phase. Furthermore, we identified the released cytokines and activated MAPK pathway in the neurons after TBI and confirmed that KNa1.2 channel was enhanced by the MAPK pathway via stimulation of TNF-α. Subsequently, compared to WT mice, neurons from Kcnt2-/- mice showed increased neuronal excitability and Kcnt2-/- mice displayed motor deficits and enhanced seizure susceptibility, which suggested that KNa1.2 channel may be neuroprotective. Therefore, this study suggests that enhanced KNa1.2 channel, facilitated by the inflammatory response, may exert a protective role in an acute phase of the TBI model.

A MnO2 nanosheet-mediated CRISPR/Cas12a system for the detection of organophosphorus pesticides in environmental water.

Nowadays, easy, convenient, and sensitive sensing strategies are still critical for organophosphorus pesticides in environmental water samples. Herein, a novel organophosphorus pesticide (OP) assay based on acetylcholinesterase (AChE) and a MnO2 nanosheet-mediated CRISPR/Cas12a reaction is reported. The single-strand DNA (ssDNA) activator of CRISPR/Cas12a was simply adsorbed on the MnO2 nanosheets as the nanoswitches of the assay. In the absence of target OPs, AChE hydrolyzed acetylcholine (ATCh) to thiocholine (TCh), which reduced the MnO2 nanosheets to Mn2+, resulting in the release of the activator followed by activation of the CRISPR/Cas12a system. The activated Cas12a thereafter nonspecifically cleaved the FAM/BHQ1-labeled ssDNA (FQ-reporter), producing a fluorescence signal. Upon the addition of target OPs, the hydrolysis of ATCh by AChE was inhibited owing to OPs combining with AChE, and thus effective quantification of OPs could be achieved by measuring the fluorescence changes of the system. As a proof of concept, dichlorvos (DDVP) was chosen as a model OP analyte to address the feasibility of the proposed method. Attributed to the excellent trans-cleavage activity of Cas12a, the fluorescent biosensor exhibits a satisfactory limit of detection (LOD) for DDVP at 0.135 ng mL-1. In addition, the excellent recoveries for the detection of DDVP in environmental water samples demonstrate the applicability of the proposed assay in real sample research.

Efficacy and safety of autologous platelet-rich plasma for diabetic foot ulcers: a systematic review and meta-analysis.

OBJECTIVE: To investigate the efficacy and safety of autologous platelet-rich plasma (au-PRP) for diabetic foot ulcer (DFU) treatment. METHOD: We conducted database searches (MEDLINE, EMBASE, evidence-based medicine reviews: CENTRAL, PubMed, and Web of Science) and reference mining for randomised controlled trials from inception to 23 January 2022. Results were scrutinised, data were extracted and research quality was investigated by two independent authors. Primary outcome was the proportion of complete ulcer healing. Secondary outcomes included both the mean time to complete healing and the incidence of adverse events. Statistical analyses were performed in RevMan 5.4 (Cochrane, UK). Kaplan-Meier curves for time to complete healing were pooled in R software (version 4.1.2) (R Foundation, Austria). RESULTS: Of the 231 records identified, 17 studies with a total of 1303 participants (649 randomised to the au-PRP group and 654 to a standard of care (SOC) group) met the eligibility criteria and were included in our study. Compared with SOC, au-PRP appeared to promote the complete healing rate (odds ratio (OR): 2.11; 95% Confidence Interval: 1.55-2.86). Au-PRP also appeared to significantly shorten complete healing time (mean duration: -19.04 days; 95%CI: -20.46--17.61]). There was no significant difference on adverse events. Results were robust on sensitivity analyses. CONCLUSION: Based on the findings of this review and meta-analysis, Au-PRP is an effective and safe adjuvant therapy for DFUs.

Instance attack: an explanation-based vulnerability analysis framework against DNNs for malware detection.

Deep neural networks (DNNs) are increasingly being used in malware detection and their robustness has been widely discussed. Conventionally, the development of an adversarial example generation scheme for DNNs involves either detailed knowledge concerning the model (i.e., gradient-based methods) or a substantial quantity of data for training a surrogate model. However, under many real-world circumstances, neither of these resources is necessarily available. Our work introduces the concept of the instance-based attack, which is both interpretable and suitable for deployment in a black-box environment. In our approach, a specific binary instance and a malware classifier are utilized as input. By incorporating data augmentation strategies, sufficient data are generated to train a relatively simple and interpretable model. Our methodology involves providing explanations for the detection model, which entails displaying the weights assigned to different components of the specific binary. Through the analysis of these explanations, we discover that the data subsections have a significant impact on the identification of malware. In this study, a novel function preserving transformation algorithm designed specifically for data subsections is introduced. Our approach involves leveraging binary diversification techniques to neutralize the effects of the most heavily-weighted section, thus generating effective adversarial examples. Our algorithm can fool the DNNs in certain cases with a success rate of almost 100%. Instance attack exhibits superior performance compared to the state-of-the-art approach. Notably, our technique can be implemented in a black-box environment and the results can be verified utilizing domain knowledge. The model can help to improve the robustness of malware detectors.

Overexpress miR-132 in the Brain Parenchyma by a Non-invasive Way Improves Tissue Repairment and Releases Memory Impairment After Traumatic Brain Injury.

Traumatic brain injury (TBI) is a serious public health problem worldwide, which could lead to an extremely high percentage of mortality and disability. Current treatment strategies mainly concentrate on neuronal protection and reconstruction, among them, exogenous neural stem cell (NSC) transplantation has long been regarded as the most effective curative treatment. However, due to secondary trauma, transplant rejection, and increased incidence of brain malignant tumor, a non-invasive therapy that enhanced endogenous neurogenesis was more suitable for TBI treatment. Our previous work has shown that miR-132 overexpression could improve neuronal differentiation of NSCs in vitro and in vivo. So, we engineered a new kind of AAV vector named AAV-PHP.eB which can transfect brain parenchyma through intravenous injection to overexpress miR-132 in brain after TBI. We found that miR-132 overexpression could reduce impact volume, promote neurogenesis in the dentate gyrus (DG), accelerate neuroblast migrating into the impact cortex, ameliorate microglia-mediated inflammatory reaction, and ultimately restore learning memory function. Our results revealed that AAV-PHP.eB-based miR-132 overexpression could improve endogenous tissue repairment and release clinical symptoms after traumatic brain injury. This work would provide a new therapeutic strategy for TBI treatment and other neurological disorders characterized by markable neuronal loss and memory impairment. miR-132 overexpression accelerates endogenous neurogenesis and releases TBI-induced tissue repairment and memory impairment. Controlled cortical impact onto the cortex would induce serious cortical injury and microglia accumulation in both cortex and hippocampus. Moreover, endogenous neuroblast could migrate around the injury core. miR-132 overexpression could accelerate neuroblast migration toward the injury core and decreased microglia accumulation in the ipsilateral cortex and hippocampus. miR-132 could be a suitable target on neuroprotective therapy after TBI.

The Diagnostic Value of Serum TGF-ß1, p2PSA Combined with PSA in Prostate Cancer.

Objective: To investigate the diagnostic value of transforming growth factor-ß1 (TGF-ß1), prostate-specific antigen isomer 2 (p2PSA) combined with a prostate-specific antigen (PSA) in prostate cancer (PCa). Methods: From October 1, 2019 to September 1, 2022 we enrolled a total of 90 patients with PCa90 patients with PCa in the urology department of our hospital were selected as the PCa group, 90 patients with benign prostatic hyperplasia (BPH) were selected as the BPH group, and 90 healthy people were selected as a healthy control group. The levels of TGF-ß1, p2PSA and PSA in serum were detected, and the differences in TGF-ß1, p2PSA and PSA levels among the three groups and PCa patients with different pathological parameters were compared. Univariate and Logistic regression analyses were used to analyze the independent risk factors affecting the occurrence of PCa. With pathological results as the 'gold standard', the diagnostic efficacy of TGF-ß1, p2PSA and PSA alone and their combination for PCa was analyzed by the receiver operating characteristic (ROC) curve. Results: The levels of serum PSA, p2PSA, and TGF-ß1 in the PCa group were higher than those in the BPH group and control group (P < .001), and those in BPH group were higher than those in the control group (P < .001). The serum indexes of PCa group increased with the increase of Glerson grade and TNM stage (P < .001). The serum indexes of patients with lymph and bone metastasis were significantly higher than those without lymph and bone metastasis (P < .001). Logistic regression analysis showed that PSA, p2PSA and TGF-ß1 were independent risk factors for PCa (P < .001). The area under the ROC curve (AUC) of PSA, p2PSA, TGF-ß1 and combined detection were 0.738, 0.862, 0.821 and 0.932, respectively. The AUC of combined detection was greater than that of single detection (P < .001). Conclusion: The expression levels of serum TGF-ß1, p2PSA and PSA are related to PCa and are independent risk factors for PCa. The combined detection of the three groups can improve the diagnostic efficacy of PCa. Combined testing improves diagnostic accuracy for prostate cancer, allows for early intervention, and improves patient survival and confidence in treatment options. This will significantly improve the clinical management of prostate cancer. Future studies could explore other biomarkers or molecular indicators to further improve the accuracy of diagnosis and grading of prostate cancer. Additionally, differences between different populations and subtypes can be studied to better understand the heterogeneity of prostate cancer.

Corrigendum: Synergistic effects of nab-PTX and anti-PD-1 antibody combination against lung cancer by regulating Pi3K/AKT pathway through the Serpinc1 gene.

[This corrects the article DOI: 10.3389/fonc.2022.933646.].

Polysorbate 80 as a possible allergenic component in cross-allergy to docetaxel and fosaprepitant: A literature review.

OBJECTIVE: Patients had allergies to both fosaprepitant and docetaxel with similar signs and symptoms. To explore the possible causes of allergy and whether there is cross-allergy between fosaprepitant and docetaxel, we conducted a literature review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: A systematic search of the following databases was performed: Pubmed, Embase, Cochrane Library, CINAHL, Scopus, Web of Science and Taylor & Francis. The final search was on 12 November 2022. Two investigators independently selected eligible studies and extracted data according to inclusion and exclusion criteria and assessed the methodological quality of included studies. Any disagreement was resolved by a third researcher. RESULTS: The main cause of fosaprepitant and docetaxel allergy is polysorbate 80. Fosaprepitant and docetaxel have similar allergic symptoms, mainly facial flushing (19.0%, 18.5%); erythema/dermatitis (17.2%, 1.9%); fluid retention (17.2%, 22.2%); and dyspnea, bronchospasm, shortness of breath and coughing (15.5%, 16.7%). Hypotension (1.7%, 7.4%) and decreased oxygen saturation (1.7%, 1.9%) are rare. The treatments for both allergies are similar: stop injection, oxygen, glucocorticoid, antihistamines and symptomatic treatments. CONCLUSION: Polysorbate 80 is the same allergenic component of docetaxel and fosaprepitant. The symptoms and treatments caused by the two drugs are similar. Most allergic reactions are not serious. Medications containing the same allergy ingredient need to be used with caution for patients with severe allergies to polysorbate 80.

Structural and Genetic Identification of the O-Antigen from an Escherichia coli Isolate, SD2019180, Representing a Novel Serogroup.

The O-antigen is one of the outermost surface components of Gram-negative bacteria. Its large structural variation provides the molecular basis for bacterial serological diversity. Here, we established the structure of the O-antigen from an Escherichia coli strain, SD2019180, which appeared to be completely different from the known E. coli serogroups. The O-antigen tetrasaccharide biological repeating unit was identified as → 2)-[ß-d-GlcpA-(1 → 4)]-[α-d-Galp-(1 → 3)]-α-l-Fucp-(1 → 3)-α-d-GlcpNAc-(1 →. Furthermore, we analyzed the O-antigen gene cluster of SD2019180 and confirmed its role in O-antigen synthesis by using deletion and complementation experiments. Our findings indicate that SD2019180 is a novel serogroup of Escherichia coli.

Suppression of SAMSN1 contributes to neuroprotection in neonatal rats suffering from hypoxic-ischemic encephalopathy injury.

This article aims to detect the effect of SAM domain, SH3 domain, and nuclear localization signal 1 (SAMSN1) in neonatal rats with neurological dysfunction induced by hypoxia and ischemia (HI). The HI model was created using 7-day postnatal rats. Zea-longa score was utilized to validate the neurological injury after HI. Then, the differentially expressed genes (DEGs) were detected by gene sequencing and bioinformatics analysis methods. The oxygen and glucose deprivation (OGD) models were established in the SY5Y cells and fetal human cortical neurons. In addition, SAMSN1-small interfering RNA, methyl thiazolyl tetrazolium assay, and cell growth curve were employed to evaluate the cell viability variation. Obviously, Zea-longa scores increased in rats with HI insult. Subsequently, SAMSN1 was screened out, and it was found that SAMSN1 was strikingly upregulated in SY5Y cells and fetal neurons post-OGD. Interestingly, we found that SAMSN1 silencing could markedly enhance cell viability and cell growth after OGD. These data suggested that downregulation of SAMSN1 may exert a neuroprotective effect on damaged neurons after HI by improving cell viability and cell survival, which provides a potential theoretical basis for clinical trials in the future to treat neonatal hypoxic-ischemic encephalopathy.

A ternary oxygen-vacancy abundant ZnMn2O4/MnCO3/nitrogen-doped reduced graphene oxide hybrid towards superior-performance lithium storage.

Transition metal oxides (TMOs) and metal carbonates exhibit high specific capacity, abundant reserves on Earth, and environmental friendliness as anode materials for lithium-ion batteries (LIBs). However, their poor electrical conductivity and serious volume expansion lead to rapid capacity decay. Herein, a stable and highly conductive composite of an oxygen-vacancy abundant nitrogen-doped reduced graphene oxide (NG) encapsulated ZnMn2O4/MnCO3 (ZnMn2O4/MnCO3/NG) hybrid is successfully fabricated, which can provide more spaces for rapid ion diffusion and corroborate fast electron transport. The ZnMn2O4/MnCO3/NG hybrid exhibits an incredible reversible capacity (916 mA h g-1 at 0.1 A g-1), preeminent cycling stability (800 mA h g-1 at 1 A g-1 after 300 cycles) and outstanding rate capability (459 mA h g-1 at 2 A g-1). The excellent lithium storage performance of ZnMn2O4/MnCO3/NG is attributed to the synergistic effect between ZnMn2O4 and MnCO3, the addition of nitrogen and oxygen defects, and the stable structures of NG, which relieve the volume expansion of the electrode material, improve the electronic conductivity and enhance structural stability and surface capacitive response. This work provides a new idea for constructing oxygen-vacancy abundant NG encapsulated bimetal oxides for energy storage of LIBs.