Clinical and pathogen features of COVID-19-associated infections during an Omicron strain outbreak in Guangzhou, China.

Although the Omicron variant has been associated with greater transmissibility and tropism of the upper respiratory tract, the clinical and pathogenic features of patients infected with the Omicron variant during an outbreak in China have been unclear. Adults with COVID-19 were retrospectively enrolled from seven medical centers in Guangzhou, China, and clinical information and specimens ( BALF, sputum, and throat swabs) from participants were collected. Conventional detection methods, metagenomics next-generation sequencing (mNGS), and other methods were used to detect pathogens in lower respiratory tract samples. From December 2022 to January 2023, we enrolled 836 patients with COVID-19, among which 56.7% patients had severe/critical illness. About 91.4% of patients were infected with the Omicron strain (BA.5.2). The detection rate of possible co-infection pathogens was 53.4% by mNGS, including Klebsiella pneumoniae (16.3%), Aspergillus fumigatus (12.2%), and Pseudomonas aeruginosa (11.8%). The co-infection rate was 19.5%, with common pathogens being Streptococcus pneumoniae (11.5%), Haemophilus influenzae (9.2%), and Adenovirus (6.9%). The superinfection rate was 75.4%, with common pathogens such as Klebsiella pneumoniae (26.1%) and Pseudomonas aeruginosa (19.4%). Klebsiella pneumoniae (27.1%% vs 6.1%, P < 0.001), Aspergillus fumigatus (19.6% vs 5.3%, P = 0.001), Acinetobacter baumannii (18.7% vs 4.4%, P = 0.001), Pseudomonas aeruginosa (16.8% vs 7.0%, P = 0.024), Staphylococcus aureus (14.0% vs 5.3%, P = 0.027), and Streptococcus pneumoniae (0.9% vs 10.5%, P = 0.002) were more common in severe cases. Co-infection and superinfection of bacteria and fungi are common in patients with severe pneumonia associated with Omicron variant infection. Sequencing methods may aid in the diagnosis and differential diagnosis of pathogens. IMPORTANCE: Our study has analyzed the clinical characteristics and pathogen spectrum of the lower respiratory tract associated with co-infection or superinfection in Guangzhou during the outbreak of the Omicron strain, particularly after the relaxation of the epidemic prevention and control strategy in China. This study will likely prompt further research into the specific issue, which will benefit clinical practice.

Monoexponential and advanced diffusion-weighted imaging for hepatic fibrosis staging based on high inter-examiner reliability.

OBJECTIVES: To determine the diagnostic efficiencies of multiple diffusion-weighted imaging (DWI) techniques for hepatic fibrosis (HF) staging under the premise of high inter-examiner reliability. METHODS: Participants with biopsy-confirmed HF were recruited and divided into the early HF (EHF) and advanced HF (AHF) groups; healthy volunteers (HVs) served as controls. Two examiners analyzed intravoxel incoherent motion (IVIM) using the IVIM-DWI and diffusion kurtosis imaging (DKI) models. Intravoxel incoherent motion-DWI, DKI, and diffusion tensor imaging parameters with intraclass correlation coefficients (ICCs) of ≥0.6 were used to create regression models: HVs vs. EHF and EHF vs. AHF. RESULTS: We enrolled 48 HVs, 59 EHF patients, and 38 AHF patients. Mean, radial, and axial kurtosis; fractional anisotropy; mean, radial, and axial diffusivity; and α exhibited excellent reliability (ICCs: 0.80-0.98). Fractional anisotropy of kurtosis, f, and apparent diffusion coefficient showed good reliability (ICCs: 0.69-0.92). The real (0.58-0.67), pseudo- (0.27-0.76), and distributed diffusion coefficients (0.58-0.67) showed low reliability. In the HVs versus (vs.) EHF model, α (p=0.008) and ADC (p=0.011) presented statistical differences (area under curve [AUC]: 0.710). In the EHF vs. AHF model, α (p=0.04) and distributed diffusion coefficient (p=0.02) presented significant differences (AUC: 0.758). CONCLUSION: Under the premise of high inter-examiner reliability, DWI and IVIM-derived stretched-exponential model parameters may help stage HF.

Ti3C2 quantum dots-modified oxygen-vacancy-rich BiOBr hollow microspheres toward optimized photocatalytic performance.

The Ti3C2 quantum dots (QDs)/oxygen-vacancy-rich BiOBr hollow microspheres composite photocatalyst was prepared using solvothermal synthesis and electrostatic self-assembly techniques. Together, Ti3C2QDs and oxygen vacancies (OVs) enhanced photocatalytic activity by broadening light absorption and improving charge transfer and separation processes, resulting in a significant performance boost. Meanwhile, the photocatalytic efficiency of Ti3C2 QDs/BiOBr-OVs is assessed to investigate its capability for oxygen evolution and degradation of tetracycline (TC) and Rhodamine B (RhB) under visible-light conditions. The rate of oxygen production is observed to be 5.1 times higher than that of pure BiOBr-OVs, while the photocatalytic degradation rates for TC and RhB is up to 97.27% and 99.8%, respectively. The synergistic effect between Ti3C2QDs and OVs greatly enhances charge separation, leading to remarkable photocatalytic activity. Furthermore, the hollow microsphere contributes to the enhanced photocatalytic performance by facilitating multiple light scatterings and providing ample surface-active sites. The resultant Ti3C2QDs/BiOBr-OVs composite photocatalyst demonstrates significant potential for environmental applications.

Curcumin for gastric cancer: Mechanism prediction via network pharmacology, docking, and in vitro experiments.

BACKGROUND: Curcumin originates from the natural herb turmeric, and its antitumor effects have been known about for a long time. However, the mechanism by which curcumin affects gastric cancer (GC) has not been elucidated. AIM: To elucidate the potential mechanisms of curcumin in the treatment of GC. METHODS: Network pharmacological approaches were used to perform network analysis of Curcumin. We first analyzed Lipinski's Rule of Five for the use of Curcumin. Curcumin latent targets were predicted using the PharmMapper, SwissTargetPrediction and DrugBank network databases. GC disease targets were mined through the GeneCard, OMIM, DrugBank and TTD network databases. Then, GO enrichment, KEGG enrichment, protein-protein interaction (PPI), and overall survival analyses were performed. The results were further verified through molecular docking, differential expression analysis and cell experiments. RESULTS: We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets. The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways. Following PPI analysis, 6 hub targets were identified, namely, estrogen receptor 1 (ESR1), epidermal growth factor receptor (EGFR), cytochrome P450 family 3 subfamily A member 4 (CYP3A4), mitogen-activated protein kinase 14 (MAPK14), cytochrome P450 family 1 subfamily A member 2 (CYP1A2), and cytochrome p450 family 2 subfamily B member 6 (CYP2B6). These factors are correlated with decreased survival rates among patients diagnosed with GC. Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes. The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation. mRNA levels of hub targets CYP3A4, MAPK14, CYP1A2, and CYP2B6 in BGC-823 cells were significantly increased in each dose group. CONCLUSION: Curcumin can play an anti-GC role through a variety of targets, pathways and biological processes.

Identification of histopathological classification and establishment of prognostic indicators of gastric adenocarcinoma based on deep learning algorithm.

The aim of this study is to establish a deep learning (DL) model to predict the pathological type of gastric adenocarcinoma cancer based on whole-slide images(WSIs). We downloaded 356 histopathological images of gastric adenocarcinoma (STAD) patients from The Cancer Genome Atlas database and randomly divided them into the training set, validation set and test set (8:1:1). Additionally, 80 H&E-stained WSIs of STAD were collected for external validation. The CLAM tool was used to cut the WSIs and further construct the model by DL algorithm, achieving an accuracy of over 90% in identifying and predicting histopathological subtypes. External validation results demonstrated the model had a certain generalization ability. Moreover, DL features were extracted from the model to further investigate the differences in immune infiltration and patient prognosis between the two subtypes. The DL model can accurately predict the pathological classification of STAD patients, and provide certain reference value for clinical diagnosis. The nomogram combining DL-signature, gene-signature and clinical features can be used as a prognostic classifier for clinical decision-making and treatment.

The topical application of Sphistin12-38 in combination with sponge spicules for the acne treatment.

We demonstrated for the first time that a marine-derived antimicrobial peptide (AMP), Sph12-38, exhibit high antimicrobial activity against P. acnes with a minimum bactericidal concentration (MBC) value of 7 µM. Meanwhile, Sph12-38 has no significant cytotoxicity to human keratinocytes (HKs) at its high concentration (33.5 µM). The topical application of sponge Haliclona sp. spicules (SHS) dramatically enhanced the skin penetration of Sph12-38 up to 40.9 ± 5.9% (p < 0.01), which was 6.1 ± 0.9-fold higher than that of Sph12-38 alone. Further, SHS resulted in the accumulation of most Sph12-38 in viable epidermis and dermis. Further, the combined use of Sph12-38 and SHS resulted in a cure rate of 100% for rabbit ear acne treatment in vivo for two weeks, while the one induced by other groups was 40%, 0% and 0% for SHS alone, Sph12-38 alone and control group, respectively. The strategy of combined using AMP and SHS can also be applied in a rational designed topical delivery system for the management of other deep infection of the skin. The effectiveness of SHS by itself on the treatment of acne was also demonstrated by clinical trials. After 14 days of treatment by 1% SHS gel. The number of skin lesions decreased by 51.4%.

Environmental toxins and reproductive health: Unraveling the effects on Sertoli cells and the blood-testis barrier in animals.

Environmental pollution is an inevitable ecological issue accompanying the process of socialization, with increasing attention to its impacts on individual organisms and ecological chains. The reproductive system, responsible for transmitting genetic material in animals, is one of the most sensitive systems to environmental toxins. Research reveals that Sertoli cells are the primary target cells for the action of environmental toxins. Different environmental toxins mostly affect the blood-testis barrier and lead to male reproductive disorders by disrupting Sertoli cells. Therefore, this article provides an in-depth exploration of the toxic mechanisms of various types of environmental toxins on the male testes. It reveals the dynamic processes of tight junctions in the blood-testis barrier affected by environmental toxins and their specific roles in the reconstruction process.

Tracheoplasty should be proactively considered within the surgical strategy for treating the ring-sling complex.

BACKGROUND: To examine the safety and effectiveness of proactive tracheoplasty for pediatric ring-sling complexes. METHODS: We retrospectively collected the data from 304 children who were diagnosed with a ring-sling complex and underwent surgery at three cardiac centers in China between January 2010 and June 2023. Children were categorized into three surgical groups: concurrent sling and tracheal surgery (Group A, n=258), staged sling and tracheal surgery (Group B, n=25), and sling-only surgery (Group C, n=21). We compared perioperative clinical characteristics, tracheal morphology changes, and outcomes across the groups. RESULTS: The median age of the children was 1.2 (IQR: 0.7-1.9) years. The anomalous tracheobronchial arborization rates were higher in Groups A (52.5%) and B (60.0%) than in Group C (15.0%). The preoperative narrow-wide ratio (NWR) was lower in Groups A and B than in Group C, with values of 0.44 (IQR: 0.35-0.52), 0.44 (0.33-0.59), and 0.68 (0.54-0.72), respectively (P<0.001). Preoperative subcarina angles were similar among the groups (P=0.54). After specific surgeries, the NWR and subcarina angle significantly improved in Groups A and B but not in Group C. There were seven in-hospital deaths and two post-discharge deaths. Respiratory symptoms improved in Groups A and B but seven children in Group C remained respiratory dysfunction. Six children presented with residual stenosis of the left pulmonary artery. CONCLUSION: Concurrent sling and tracheal surgeries for children with the ring-sling complex are safe and effective and are especially preferable for those with NWR ≤0.6, long-segment or diffuse tracheal stenosis, anomalous tracheobronchial arborization, and pronounced respiratory symptoms.

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

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

Comparative Proteomic Identification of Ram Sperm before and after In Vitro Capacitation.

Ram sperm undergo a sequence of physiological and biochemical changes collectively termed as capacitation to perform oocyte fertilization. However, the protein changes induced by capacitation remain in need of further exploration. Thus, the present study investigated the comparative proteomic profiling in ram spermatozoa under non-capacitating (NC) and capacitating (CAP) conditions in vitro using a liquid chromatography-tandem mass spectrometry combined with tandem mass tag labeling strategy. As a results, 2050 proteins were identified and quantified; 348 of them were differentially abundant, with 280 of the proteins upregulated and 68 of the proteins downregulated between the CAP and NC spermatozoa, respectively. Functional enrichment analysis indicated that the differentially abundant proteins Prune Exopolyphosphatase 1, Galactose-1-Phosphate Uridylyltransferase, and ATP Citrate Lyase were strictly related to energy production and conversion, and Phosphoglycolate phosphatase, Glucosamine-6-Phosphate Deaminase 1 and 2 were related to metabolism, RNA processing, and vesicular transport pathways. Furthermore, the networks of protein-protein interaction indicated a strong interaction among these differential proteins in annotated pathways such as ubiquitin and transport metabolism. Our findings indicate that capacitation progress might be regulated through different pathways, providing insights into mechanisms involved in ram sperm capacitation and fertility.

Fabrication of Single-Ion Conductors Based on Liquid Crystal Polymer Network for Quasi-Solid-State Lithium Ion Batteries.

Single-ion conductive polymer electrolytes can improve the safety of lithium ion batteries (LIBs) by increasing the lithium transference number (tLi+) and avoiding the growth of lithium dendrites. Meanwhile, the self-assembled ordered structure of liquid crystal polymer networks (LCNs) can provide specific channels for the ordered transport of Li ions. Herein, single-ion conductive nematic and cholesteric LCN electrolyte membranes (denoted as NLCN-Li and CLCN-Li) were successfully prepared. NLCN-Li was then coated on commercial Celgard 2325 while CLCN-Li was coated on poly(vinylidene fluoride-hexafluoropropylene) film, coupled with plasticizer, to make NLCN-Li/Cel and CLCN-Li/Pv quasi-solid-state electrolyte membranes, respectively. Their electrochemical properties were evaluated, and it was found that they possessed benign thermal stability and electrolyte/electrode compatibility, high tLi+ up to 0.98 and high electrochemical stability window up to 5.2 V. A small amount (0.5M) of extra Li salt added to the plasticizer could improve the ion conductivity from 1.79 × 10-5 to 5.04 × 10-4 S cm-1, while the tLi+ remained 0.85. The assembled LFP|Li batteries also exhibited excellent cycling and rate performances. The orderliness of the LCN layer played an important role in the distribution and movement of Li ions, thereby affecting the Li deposition and growth of Li dendrites. As the first report of nematic and cholesteric LCN single-ion conductors, this work sheds light on the design and fabrication of ordered quasi-solid-state electrolytes for high-performance and safe LIBs.

Efficacy and safety of oxaliplatin-based hyperthermic intraperitoneal chemotherapy with secondary cytoreduction for platinum resistant recurrent ovarian cancer: A single-center retrospective cohort study.

BACKGROUND/PURPOSE: This retrospective study evaluated the efficacy and adverse effects of oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) with secondary cytoreductive surgery (CRS) in patients with recurrent ovarian cancer. METHODS: Patients diagnosed with recurrent epithelial ovarian cancer, including fallopian tube and peritoneal origin, who underwent oxaliplatin-based HIPEC with secondary CRS, were enrolled. The primary outcome was progression-free survival (PFS), and the secondary outcomes were overall survival (OS) and adverse events. RESULTS: A total of 33 patients were included in the analysis. The mean PFS and OS were 20.4 months (95% CI 16.3-24.5 months) and 26.7 months (95% CI 23.7-29.7), respectively. Furthermore, the OS and PFS between platinum-sensitive and resistant recurrence showed no significant difference. Univariate and multivariate analysis of PFS identified a pre-operative peritoneal carcinomatosis index (PCI) score of ≥5 as a poor prognostic factor. Among them, the incidence of acute kidney injury was 9.0 % & none had grade ≧3 adverse events. CONCLUSION: Oxaliplatin-based HIPEC with secondary CRS might provide a survival benefit for patients with recurrent ovarian cancer with a decreased incidence of renal toxicity compared to cisplatin-based regimens. It might be effective and feasible in selected recurrent ovarian cancer patients, regardless of platinum-sensitive or resistant.

A three-stage wavelength selection algorithm for near-infrared spectroscopy calibration.

The near-infrared spectral data is highly high dimensional and contains redundant information, it is necessary to identify the most representative characteristic wavelengths before modeling to improve model accuracy and reliability. At present, there are many methods for selecting the characteristic wavelengths of NIR spectroscopy, but the collinearity among wavelengths is still a main issue that leads to poor model effects. Therefore, this study proposes a three-stage wavelength selection algorithm (Stage III) to reduce redundancy in NIR spectral data and collinearity between wavelength variables, resulting in a simpler and more accurate predictive model. The research uses a public NIR data set of corn samples as its subject. Initially, the wavelengths with the higher correlation coefficients are chosen after calculating the relationship coefficients between every wavelength vector and the concentration vector. On this basis, the correlation coefficients between the vectors of each wavelength point are calculated, and those wavelength points with smaller correlation coefficients with other wavelength points are selected. Ultimately, the stepwise regression analysis selects the wavelengths that provide substantial value to the model as the variables for modeling, leading to the development of a multiple linear regression model. The results show that the model using the three-stage wavelength selection algorithm outperforms those using the full spectrum, Stages I and Stage II, and the coefficient of determination of the test set of the Stage III-MLR model achieved an accuracy of 0.9360. Instead of the successive projections algorithm (SPA), uninformative variable elimination (UVE), and competitive adaptive reweighted sampling (CARS), Stage III is better in the model prediction accuracy. Therefore, the three-stage wavelength selection algorithm is an effective wavelength selection algorithm that can effectively model NIR spectroscopy, reduce the collinearity between the wavelength variables, simplify the complexity of the model, and improve the prediction precision of the model.

Efficacy and safety of efdamrofusp alfa versus aflibercept in participants with neovascular age-related macular degeneration: a randomized, double-masked, active-controlled, non-inferiority, phase 2 trial.

PURPOSE: To evaluate efficacy and safety of efdamrofusp alfa compared with aflibercept in neovascular age-related macular degeneration (nAMD). DESIGN: Randomized, double-masked, multicenter, active-controlled, non-inferiority phase 2 study PARTICIPANTS: A total of 231 treatment-naïve and previously treated participants with active choroidal neovascularization secondary to nAMD were enrolled. METHODS: Eligible participants were randomized (1:1:1) to 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa or 2 mg aflibercept groups. Participants in all groups received three initial monthly loading doses, followed by treatment every 8 weeks with assessment every 4 weeks up to week 52. MAIN OUTCOME MEASURES: The primary endpoint was the mean BCVA change from baseline to week 36. The pre-specified noninferiority margin was set as -5 letters (80% CI). RESULTS: Each treatment group included 77 participants. The mean BCVA changes from baseline to week 36 for 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa and aflibercept groups were +10.6, +11.4, +12.0 letters, respectively; Least Squares (LS) mean difference were -1.4 (80% CI: -3.5 to 0.7) between 2 mg efdamrofusp alfa and aflibercept, and -0.6 (80% CI: -2.7 to 1.6) between 4 mg efdamrofusp alfa and aflibercept. Mean central retinal thickness changes were consistent across groups. Adverse event rate was comparable among the groups. CONCLUSIONS: Efdamrofusp alfa demonstrated noninferiority to aflibercept in BCVA improvement, accompanied by a similar safety profile.

Multigenerational effects of disperse blue 79 at environmentally relevant concentrations on zebrafish (Danio rerio) fecundity: An integrated approach.

The brominated azo dye (BAD) Disperse Blue (DB79) is a widespread environmental pollutant. The long-term toxicological effects of DB79 and the mechanisms thereof must be understood to allow assessment of the risks of DB79 pollution. A dual-omics approach employing in silico analysis, bioinformatics, and in vitro bioassays was used to investigate the transgenerational (F0-F2) toxicity of DB79 in zebrafish at environmentally relevant concentrations and identify molecular initiating events and key events associated with DB79-induced fertility disorders. Exposure to 500 µg/L DB79 decreased fecundity in the F0 and F1 generations by > 30 % and increased the condition factor of the F1 generation 1.24-fold. PPARα/RXR and PXR ligand binding activation were found to be critical molecular initiating events associated with the decrease in fecundity. Several key events (changes in fatty acid oxidation and uptake, lipoprotein metabolism, and xenobiotic metabolism and transport) involved in lipid dysregulation and xenobiotic disposition were found to be induced by DB79 through bioinformatic annotation using dual-omics data. The biomolecular underpinnings of decreased transgenerational fertility in zebrafish attributable to BAD exposure were elucidated and novel biomolecular targets in the adverse outcome pathway framework were identified. These results will inform future studies and facilitate the development of mitigation strategies.

The E3 ubiquitin ligase FBXO38 maintains the antitumor function of natural killer cells by sustaining IL-15R signaling.

Natural killer (NK) cells are the main innate antitumor effector cells but their function is often constrained in the tumor microenvironment (TME). It has been reported that the E3 ligase FBXO38 accelerates PD-1 degradation in tumor-infiltrating T cells to unleash their cytotoxic function. In this study, we found that the transcriptional levels of FBXO38 in intratumoral NK cells of cancer patients and tumor-bearing mice were significantly lower than in peritumoral NK cells. Conditional knock-out (cKO) of FBXO38 in NK cells accelerated tumor growth and increased tumor metastasis. FBXO38 deficiency resulted in impaired proliferation and survival of tumor-infiltrating NK (TINK) cells. Mechanistically, FBXO38 deficiency enhanced TGF-ß signaling, including elevating expression of Smad2 and Smad3, which suppressed expression of the transcription factor Eomes and further reduced expression of surface IL-15Rß and IL-15Rγc on NK cells. Consequently, FBXO38 deficiency led to TINK cell hyporesponsiveness to IL-15. Consistent with these observations, FBXO38 mRNA expression was positively correlated with the proliferation of TINK cells in multiple human tumors. To study the therapeutic potential of FBXO38, mice bearing human tumors were treated with FBXO38 overexpressed human primary NK cells and showed a significant reduction in tumor size and prolonged survival. In conclusion, our results suggest that FBXO38 sustains NK-cell expansion and survival to promote antitumor immunity, and have potential therapeutic implications as they suggest FBXO38 could be harnessed to enhance NK cell-based cancer immunotherapy.