O-GlcNAcylation promotes topoisomerase IIα catalytic activity in breast cancer chemoresistance.

DNA topoisomerase IIα (TOP2A) plays a vital role in replication and cell division by catalytically altering DNA topology. It is a prominent target for anticancer drugs, but clinical efficacy is often compromised due to chemoresistance. In this study, we investigate the role of TOP2A O-GlcNAcylation in breast cancer cells and patient tumor tissues. Our results demonstrate that elevated TOP2A, especially its O-GlcNAcylation, promotes breast cancer malignant progression and resistance to adriamycin (Adm). O-GlcNAcylation at Ser1469 enhances TOP2A chromatin DNA binding and catalytic activity, leading to resistance to Adm in breast cancer cells and xenograft models. Mechanistically, O-GlcNAcylation-modulated interactions between TOP2A and cell cycle regulators influence downstream gene expression and contribute to breast cancer drug resistance. These results reveal a previously unrecognized mechanistic role for TOP2A O-GlcNAcylation in breast cancer chemotherapy resistance and provide support for targeting TOP2A O-GlcNAcylation in cancer therapy.

Involvement of expanded cytotoxic and proinflammatory CD28null T cells in primary Sjögren's syndrome.

OBJECTIVE: The absence of CD28 is a feature of antigen-experienced, highly differentiated and aged T cells. The pathogenicity of CD28null T cells remains elusive in primary Sjögren's syndrome (pSS). Therefore, this study was performed to explore the characteristics of CD28null T cells in both peripheral blood and minor salivary glands (MSGs) of pSS patients. METHODS: pSS patients and paired healthy controls (HCs) were enrolled. The phenotype of peripheral CD28null T cells was analyzed using flow cytometry. In vitro functional assays were performed to evaluate the cytotoxic and proinflammatory effects of peripheral CD28null T cells. In addition, polychromatic immunofluorescence staining was performed to investigate infiltrating CD28null T cells in MSGs. RESULTS: A significant expansion of peripheral CD28null T cells was observed in pSS patients compared with HCs (p < 0.001), which were primarily CD8+CD28null T cells. The proportion of peripheral CD8+CD28null T cells moderately correlated with the erythrocyte sedimentation rate (r = 0.57, p < 0.01) and IgG levels (r = 0.44, p < 0.01). Peripheral CD28null T cells had stronger capacities to secrete granzyme B and perforin, but comparable capacities to secrete IFN-γ and TNF-α than their CD28+ counterparts. An abundant amount of cytotoxic and pro-inflammatory CD28null T cells was also found in MSGs. Moreover, a high expression of the chemokine receptor CXCR3 was found on peripheral and tissue-resident CD28null T cells, with its ligands CXCL9/10 abundantly present in MSGs. CONCLUSION: Increasing CD28null T cells with strong cytotoxicity and proinflammatory effects were observed in both peripheral blood and MSGs from pSS patients. The precise mechanism of action and migration still needs further investigation.

Topographic metabolism-function relationships in Alzheimer's disease: A simultaneous PET/MRI study.

Disruptions of neural metabolism and function occur in parallel during Alzheimer's disease (AD). While many studies have shown diverse metabolic-functional relationships in specific brain regions, much less is known about how large-scale network-level functional activity is associated with the topology of metabolism in AD. In this study, we took the advantages of simultaneous PET/MRI and multivariate analyses to investigate the associations between AD-related stereotypical spatial patterns (topographies) of glucose metabolism, measured by fluorodeoxyglucose PET, and functional connectivity, measured by resting-state functional MRI. A total of 101 participants, including 37 patients with AD, 25 patients with mild cognitive impairment (MCI), and 39 cognitively normal controls, underwent PET/MRI scans and cognitive assessments. Three pairs of distinct but optimally correlated metabolic and functional topographies were identified, encompassing large-scale networks including the default-mode, executive and control, salience, attention, and subcortical networks. Importantly, the metabolic-functional associations were not only limited to one-to-one-corresponding regions, but also occur in remote and non-overlapping regions. Furthermore, both glucose metabolism and functional connectivity, as well as their linkages, exhibited various degrees of disruptions in patients with MCI and AD, and were correlated with cognitive decline. In conclusion, our results support distributed and heterogeneous topographic associations between metabolism and function, which are jeopardized by AD. Findings of this study may deepen our understanding of the pathological mechanism of AD through the perspectives of both local energy efficiency and long-term interactions between synaptic disruption and functional disconnection contributing to the clinical symptomatology in AD.

Generation of streptocarbazoles with cytotoxicities by pathway engineering and insights into their biosynthesis.

Streptocarbazoles are a class of indolocarbazole (ICZ) compounds produced by Streptomyces strains that feature unique cyclic N-glycosidic linkages between the 1,3-carbon atoms of the glycosyl moiety and the two indole nitrogen atoms. Although several streptocarbazole compounds display effective cytotoxic activity, their biosynthesis remains unclear. Herein, through the inactivation of the aminotransferase gene spcI in the staurosporine biosynthetic gene cluster spc followed by heterologous expression, two new streptocarbazole derivatives (1 and 3) and three known ICZs (2, 4, and 5) were generated. Their structures were determined by a combination of spectroscopic methods, circular dichroism measurements, and single-crystal X-ray diffraction. Compounds 1-4 displayed moderate cytotoxicity against HCT-116 cell line, and compounds 3 and 4 were effective against Huh 7 cell line. Double-gene knockout experiments allowed us to propose a biosynthetic pathway for streptocarbazole productions. Furthermore, by overexpression of the involving key enzymes, the production of streptocarbazoles 1 and 3 were improved by approximately 1.5-2.5 fold. IMPORTANCE: Indolocarbazoles (ICZs) are a group of antitumor agents, with several analogs used in clinical trials. Therefore, the identification of novel ICZ compounds is important for drug discovery. Streptocarbazoles harbor unique N-glycosidic linkages (N13-C1' and N12-C3'), distinguishing them from the representative ICZ compound staurosporine; however, their biosynthesis remains unclear. In this study, two new streptocarbazoles (1 and 3) with cytotoxic activities were obtained by manipulating the staurosporine biosynthetic gene cluster spc followed by heterologous expression. The biosynthetic pathway of streptocarbazoles was proposed, and their productions were improved through the overexpression of the key enzymes involved. This study enriches the structural diversity of ICZ compounds and would facilitate the discovery of new streptocarbazoles via synthetic biological strategies.

Distinct phenotype and prognosis of immune-mediated necrotizing myopathy based on clinical-serological-pathological classification.

OBJECTIVE: The aim of the study was to investigate the characteristics and prognosis of patients with immune-mediated necrotizing myopathy (IMNM) based on clinical, serological and pathological classification. METHODS: A total of 138 patients with IMNM who met the 2018 European Neuromuscular Center criteria for IMNM including 62 anti-SRP, 32 anti-HMGCR-positive and 44 myositis specific antibody-negative were involved in the study. All patients were followed up and evaluated remission and relapse. Clustering analysis based on clinical, serological, and pathological parameters was used to define subgroups. RESULTS: Clustering analysis classified IMNM into three clusters. Cluster 1 patients (n = 35) had the highest CK levels, the shortest disease course, severe muscle weakness, and more inflammation infiltration in muscle biopsy. Cluster 2 patients (n = 79) had the lowest CK level and moderate inflammation infiltrate. Cluster 3 patients (n = 24) had the youngest age of onset, the longest disease course and the least frequency of inflammatory infiltration. Patients in cluster 3 had the longest time-to-remission (median survival time: 61[18.3, 103.7] vs 20.5[16.2, 24.9] and 27[19.6, 34.3] months) and shortest relapse-free time than those in cluster 1 and 2 (median remission time 95%CI: 34[19.9, 48.0] vs 73[49.0, 68.7] and 73[48.4, 97.6] months). Patients with age of onset >55 years, more regeneration of muscle fibers, more CD4+T infiltration, and MAC deposition had more favorable outcomes regarding time to achieving remission. CONCLUSIONS: Stratification combining clinical, serological, and pathological features could distinguish phenotypes and prognosis of IMNM. The pathological characteristics may impact the long-term prognosis of patients with IMNM.

Hemoadsorption in acute respiratory distress syndrome patients requiring venovenous extracorporeal membrane oxygenation: a systematic review.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV ECMO) has been widely used for severe acute respiratory distress syndrome (ARDS) in recent years. However, the role of hemoadsorption in ARDS patients requiring VV ECMO is unclear. METHODS: Therefore, we conducted a systematic review to describe the effect of hemoadsorption on outcomes of ARDS patients requiring VV ECMO and elucidate the risk factors for adverse outcomes. We conducted and reported a systematic literature review based on the principles derived from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The systematic review searched Embase, CINHAL, and Pubmed databases for studies on ARDS patients receiving hemoadsorption and VV ECMO. The demographic data, clinical data and biological data of the patients were collected. RESULTS: We ultimately included a total of 8 articles including 189 patients. We characterized the population both clinically and biologically. Our review showed most studies described reductions in inflammatory markers and fluid resuscitation drug dosage in ARDS patients with Coronavirus disease 2019 (COVID-19) or sepsis after hemoadsorption. CONCLUSION: Because most of the studies have the characteristics of high heterogeneity, we could only draw very cautious conclusions that hemoadsorption therapy may enhance hemodynamic stability in ARDS patients with COVID-19 or sepsis receiving VV ECMO support. However, our results do not allow us to draw conclusions that hemoadsorption could reduce inflammation and mortality. Prospective randomized controlled studies with a larger sample size are needed in the future to verify the role of hemoadsorption in ARDS patients requiring VV ECMO.

Identifying the Stripping of Oxide Debris from Graphene Oxide: Evidence from Experimental Analysis and Molecular Simulation.

In this study, characteristics of oxidation debris (OD) and its stripping mechanism from graphene oxide (GO) were explored. The results demonstrated that OD contains three components, namely, protein-, fulvic acid-, and humic acid-like substances; among these, protein-like substances with lower molecular weight and higher hydrophilicity were most liable to be stripped from GO and were the primary components stripped from GO at pH < 10, whereas humic acid- and fulvic acid-like substances were stripped from GO at pH > 10. During the stripping of OD, hydrogen bonds from carboxyl and carbonyl were the first to break, followed by hydrogen bonds from epoxy. Subsequently, π-π interactions were broken, and hydrogen bond interactions induced by hydroxyl groups were the hardest to break. After the stripping of OD, the recombination of OD on GO was observed, and regions containing relatively fewer oxygen-containing functional groups were favorable binding sites for the readsorbed OD. The stripping and recombination of OD on GO resulted in an uneven GO surface, which should be considered during the development of GO-based environmental materials and the evaluation of their environmental behavior.

Synergistic effects of achieving perinatal interventions on bronchopulmonary dysplasia in preterm infants.

To investigate the effect of perinatal interventions on the risk of severe BPD (sBPD) and death in extremely preterm infants (EPIs) and their synergistic effects. This was a secondary analysis of the prospective cohort Chinese Neonatal Network (CHNN). Infants with a birth weight of 500 to 1250 g or 24-28 weeks completed gestational age were recruited. The impacts and the synergistic effects of six evidence-based perinatal interventions on the primary outcomes of sBPD and death were assessed by univariate and multivariable logistic regression modeling. Totally, 6568 EPIs were finally enrolled. Antenatal corticosteroid (adjusted OR, aOR, 0.74; 95%CI, 0.65-083), birth in centers with tertiary NICU (aOR, 0.64; 95%CI, 0.57-0.72), preventing intubation in the delivery room (aOR, 0.65; 95%CI, 0.58-0.73), early caffeine therapy (aOR, 0.59; 95%CI, 0.52-0.66), and early extubating (aOR, 0.42; 95%CI 0.37-0.47), were strongly associated with a lower risk of sBPD and death while early surfactant administration was associated with a lower risk of death (aOR, 0.84; 95%CI, 0.72, 0.98). Compared with achieving 0/1 perinatal interventions, achieving more than one intervention was associated with decreased rates (46.6% in 0/1 groups while 38.5%, 29.6%, 22.2%, 16.2%, and 11.7% in 2/3/4/5/6-intervention groups respectively) and reduced risks of sBPD/death with aORs of 0.76(0.60, 0.96), 0.55(0.43, 0.69), 0.38(0.30, 0.48), 0.28(0.22, 0.36), and 0.20(0.15, 0.27) in 2, 3, 4, 5, and 6 intervention groups respectively. Subgroup analyses showed consistent results. CONCLUSION: Six perinatal interventions can effectively reduce the risk of sBPD and death in a synergistic form. WHAT IS KNOWN: • Bronchopulmonary dysplasia (BPD) is a multifactorial chronic lung disease associated with prematurity. The effective management of BPD requires a comprehensive set of interventions. However, the extent to which these interventions can mitigate the risk of severe outcomes, such as severe BPD or mortality, or if they possess synergistic effects remains unknown. WHAT IS NEW: • The implementation of various perinatal interventions, such as prenatal steroids, birth in centers with tertiary NICU, early non-Invasive respiratory support, surfactant administration within 2 hours after birth, early caffeine initiation within 3 days, and early extubation within 7 days after birth has shown promising results in the prevention of severe bronchopulmonary dysplasia (BPD) or mortality in extremely preterm infants. Moreover, these interventions have demonstrated synergistic effects when implemented in combination.

The Discovery of Cyclic Lipopeptide Olenamidonins in a Deepsea-Derived Streptomyces Strain by Knocking Out a DtxR Family Regulator.

Three new cyclic lipopeptides, olenamidonins A-C (1-3), in addition to two previously reported metabolites (4 and 5), were accumulated in the ΔdtxRso deletion mutant of deepsea-derived Streptomyces olivaceus SCSIO 1071. The structures of these cyclic lipopeptides were determined by a combination of spectroscopic methods and circular dichroism (CD) measurement. The antibacterial assay results showed that compounds 1-5 displayed different degrees of growth inhibition against multidrug-resistant (MDR) bacterial strains Enterococcus faecalis CCARM 5172 and Enterococcus faecium CCARM 5203 with minimum inhibitory concentrations (MICs) of 1.56-6.25 µg/mL.

First Report on Apothecium Deformity of Morchella importuna Caused by Alternaria alternata in China.

Morel mushrooms (Morchella spp.) are highly regarded globally for their distinctive texture and savory flavor. In 2022, the cultivation area for morel mushrooms in China reached nearly 20,000 hectares, with predominant cultivars including M. sextelata, M. importuna and M. exima (Bian et al., 2024). In March 2022, however, deformities of friting bodies were observed in M. importna at morel mushroom farms in Huaihua city (28.43°N, 110.47°), China, with an incidence rate ranging from 5% to 10%. The disease symptoms begin with the invasion of the hymenium of morel mushroom by white cotton-like mycelia, ultimately resulting in halted fruiting body growth and the manifestation of anomalous fruiting body morphology. Infected samples were collected from the morel growers. Following sterilization with 75% ethanol of the surrounding tissue of infected samples, the white hyphae from the morel lesions were picked out using a dissecting needle, and incubated onto potato saccharose agar medium supplemented with 60 mg/L streptomycin at 25°C. Studies showed that seven out of nine fungal isolates exhibiting identical morphological features rapidly grew on the same culture medium described above, reaching a length of 75 mm in 4 to 5 days at 25°C. The white and thick hyphal colonies of these isolates gradually filled with brown spore powder. Generally, the conidia of the hyphal colonies were polyblastic with protrusions at the tips, measuring 75 to 165 × 36 to 50 µm (n = 30) in width and length, displaying colors varying from light reddish brown to grayish brown, and possessing one or five septa. To confirm the identity of the pathogen, the region of the internal transcribed spacer region (ITS), 28S nuclear ribosomal large subunit (LSU), and RNA polymerase II second largest subunit (rpb2) genes of the representative isolate H2 were amplified by PCR (Taguiam, et al. 2021). The generated ITS (OR338304), rpb2 (OR452112) and LSU (OR338334) from the isolate H2 had 98-100% similarity to the Alternaria alternata strains ATCC 6663 and CBS 880.95 in BLASTn analysis. ITS, rpb2 and LSU sequences were assembled using Sequence Matrix, and their homogeneity was assessed with PAUP (Vaidya et al., 2011). Bayesian (MrBayes-3.2.7a) and maximum-likelihood (RAxML1.3.1) methods, utilizing the best fit GTR+G+I model obtained from MrModeltest 2.3, were employed for phylogenetic analysis (Aveskamp et al. 2010). Based on morphological characteristics and phylogenetic analysis, the isolate H2 was identified as A. alternata. In the second year post-disease, disease-free morels, with a height of 3 cm, were cultivated in field greenhouses and used for test. A 15 ml suspension (1 × 106 conidia/ml) was applied to 15 young fruiting bodies and their corresponding substrate soil. The results showed that the reappearance of white cotton-like mycelia and deformed M. importuna fruiting bodies within 7 days post-inoculation with the spore suspension, as opposed to the controls. The isolates (H2-1, H2-2 and H2-3) were reisolated from the infected tissues and identified as A. alternata based on its morphological features and phylogenetic analyses. In this study, a similar investigation was previously conducted on cultivated quinoa (Chenopodium quinoa) in Eastern Denmark (Colque-Little et al., 2023). This study marks the first documentation of A. alternata causing deformities in M. importuna fruiting bodies. These deformities occur under conditions of high-temperature (>22°C) and high humidity (>88%). Our findings provide crucial insights for managing A. alternata in M. importuna cultivation in China.

Machine learning-based prediction of cadmium pollution in topsoil and identification of critical driving factors in a mining area.

Mining activities have resulted in a substantial accumulation of cadmium (Cd) in agricultural soils, particularly in southern China. Long-term Cd exposure can cause plant growth inhibition and various diseases. Rapid identification of the extent of soil Cd pollution and its driving factors are essential for soil management and risk assessment. However, traditional geostatistical methods are difficult to simulate the complex nonlinear relationships between soil Cd and potential features. In this study, sequential extraction and hotspot analyses indicated that Cd accumulation increased significantly near mining sites and exhibited high mobility. The concentration of Cd was estimated using three machine learning models based on 3169 topsoil samples, seven quantitative variables (soil pH, Fe, Ca, Mn, TOC, Al/Si and ba value) and three quantitative variables (soil parent rock, terrain and soil type). The random forest model achieved marginally better performance than the other models, with an R2 of 0.78. Importance analysis revealed that soil pH and Ca and Mn contents were the most significant factors affecting Cd accumulation and migration. Conversely, due to the essence of controlling Cd migration being soil property, soil type, terrain, and soil parent materials had little impact on the spatial distribution of soil Cd under the influence of mining activities. Our results provide a better understanding of the geochemical behavior of soil Cd in mining areas, which could be helpful for environmental management departments in controlling the diffusion of Cd pollution and capturing key targets for soil remediation.

A Versatile Thioesterase Involved in Dimerization during Cinnamoyl Lipid Biosynthesis.

The cinnamoyl lipid compound youssoufene A1 (1), featuring a unique dearomatic carbon-bridged dimeric skeleton, exhibits increased inhibition against multidrug resistant Enterococcus faecalis as compared to monomeric youssoufenes. However, the formation process of this intriguing dearomatization/dimerization remains unknown. In this study, an unusual "gene-within-gene" thioesterase (TE) gene ysfF was functionally characterized. The gene was found to naturally encodes two proteins, an entire YsfF with α/ß-hydrolase and 4-hydroxybenzoyl-CoA thioesterase (4-HBT)-like enzyme domains, and a nested YsfFHBT (4-HBT-like enzyme). Using an intracellular tagged carrier-protein tracking (ITCT) strategy, in vitro reconstitution and in vivo experiments, we found that: i) both domains of YsfF displayed thioesterase activities; ii) YsfF/YsfFHBT could accomplish the 6π-electrocyclic ring closure for benzene ring formation; and iii) YsfF and cyclase YsfX together were responsible for the ACP-tethered dearomatization/dimerization process, possibly through an unprecedented Michael-type addition reaction. Moreover, site-directed mutagenesis experiments demonstrated that N301, E483 and H566 of YsfF are critical residues for both the 6π-electrocyclization and dimerization processes. This study enhances our understanding of the multifunctionality of the TE protein family.

Enantiopure Corral[4]BINOLs as Ultrastrong Receptors for Recognition and Differential Sensing of Steroids.

The precise recognition and sensing of steroids, a type of vital biomolecules, hold immense practical value across various domains. In this study, we introduced corral[4]BINOLs (C[4]BINOLs), a pair of enantiomeric conjugated deep-cavity hosts, as novel synthetic receptors for binding steroids. Due to the strong hydrophobic effect of their deep nonpolar, chiral cavities, the two enantiomers of C[4]BINOLs demonstrated exceptionally high recognition affinities (up to 1012 M-1) for 16 important steroidal compounds as well as good enantioselectiviy (up to 15.5) in aqueous solutions, establishing them as the most potent known steroid receptors. Harnessing their ultrahigh affinity, remarkable enantioselectivity, and fluorescence emission properties, the two C[4]BINOL enantiomers were employed to compose a fluorescent sensor array which achieved discrimination and sensing of 16 structurally similar steroids at low concentrations.

Next-Generation Drug Discovery to Combat Antimicrobial Resistance.

The widespread emergence of antibiotic-resistant pathogens poses a severe threat to public health. This problem becomes even worse with a coincident decline in the supply of new antibiotics. Conventional bioactivity-guided natural product discovery has failed to meet the urgent need for new antibiotics, largely due to limited resources and high rediscovery rates. Recent advances in cultivation techniques, analytical technologies, and genomics-based approaches have greatly expanded our access to previously underexploited microbial sources. These strategies will enable us to access new reservoirs of microorganisms and unleash their chemical potentials, thus opening new opportunities for the discovery of next-generation drugs to address the growing concerns of antimicrobial resistance.

Elucidation of the Late Steps during Hexacosalactone A Biosynthesis in Streptomyces samsunensis OUCT16-12.

Hexacosalactone A (1) is a polyene macrolide compound featuring a 2-amino-3-hydroxycyclopent-2-enone (C5N)-fumaryl moiety. While compound 1 has been proposed to be assembled via a type I modular polyketide synthase (PKS) system, most of the putative biosynthetic steps lack experimental evidence. In this study, we elucidated the post-PKS tailoring steps of compound 1 through in vivo gene inactivation and in vitro biochemical assays. We demonstrated that the amide synthetase HexB and O-methyltransferase HexF are responsible for the installations of the C5N moiety and the methyl group at 15-OH of compound 1, respectively; two new hexacosalactone analogs, named hexacosalactones B (4) and C (5), were purified and structurally characterized, followed by anti-multidrug resistance (anti-MDR) bacterial assays, revealing that the C5N ring and the methyl group are necessary for the antibacterial bioactivities. Through database mining of C5N-forming proteins HexABC, six uncharacterized biosynthetic gene clusters (BGCs), putatively encoding compounds with different types of backbones, were identified, providing potentials to discover novel bioactive compounds with C5N moiety. IMPORTANCE In this study, we elucidate the post-PKS tailoring steps during the biosynthesis of compound 1 and demonstrate that both C5N and 15-OMe groups are critical for the antibacterial activities of compound 1, paving the way for generation of hexacosalactone derivatives via synthetic biology strategy. In addition, mining of HexABC homologs from the GenBank database revealed their wide distribution across the bacterial world, facilitating the discovery of other bioactive natural products with C5N moiety.

A comprehensive overview on the transmission, pathogenesis, diagnosis, treatment, and prevention of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus (SARS-CoV) is a single positive-strand RNA virus that is responsible for the current pandemic that the world has been facing since 2019. The primary route of transmission of SARS-CoV-2 is through respiratory tract transmission. However, other transmission routes such as fecal-oral, vertical transmission, and aerosol-eye also exist. In addition, it has been found that the pathogenesis of this virus involves the binding of the virus's S protein to its host cell surface receptor angiotensin-converting enzyme 2, which results in the subsequent membrane fusion that is required for SARS-CoV-2 to replicate and complete its entire life. The clinical symptoms of patients infected with SARS-CoV-2 can range from asymptomatic to severe. The most common symptoms seen include fever, dry cough, and fatigue. Once these symptoms are observed, a nucleic acid test is done using reverse transcription-polymerase chain reaction. This currently serves as the main confirmatory tool for COVID-19. Despite the fact that no cure has been found for SARS-CoV-2, prevention methods such as vaccines, specific facial mask, and social distancing have proven to be quite effective. It is imperative to have a complete understanding of the transmission and pathogenesis of this virus. To effectively develop new drugs as well as diagnostic tools, more knowledge about this virus would be needed.

Sidelobe-suppressed sub-diffraction-limit quasi-non-diffracting light sheets achieved by super-oscillatory lenses.

Sub-diffraction-limit quasi-non-diffracting light sheets (SQLSs) are crucial for a resolution-enhanced and field of view (FOV)-enlarged light sheet microscope. However, it has aways been plagued by sidelobes inducing severe background noise. Here, a self-trade-off optimized method is proposed to generate sidelobe-suppressed SQLSs based on super-oscillatory lenses (SOLs). An SQLS thus obtained shows sidelobes of only 15.4%, first realizing the sub-diffraction-limit thickness, quasi-non-diffracting characteristic, and suppressed sidelobes simultaneously for static light sheets. Moreover, a window-like energy allocation is realized by the self-trade-off optimized method, successfully further suppressing the sidelobes. In particular, an SQLS with theoretical sidelobes of 7.6% is achieved within the window, which provides a new strategy to deal with sidelobes for light sheets and shows great potential in high signal-to-noise ratio light sheet microscopy (LSM).

NIR-II-absorbing diimmonium polymer agent achieves excellent photothermal therapy with induction of tumor immunogenic cell death.

Photothermal therapy has shown great promise for cancer treatment and second near-infrared (NIR-II) -absorbing particles could further improve its precision and applicability due to its superior penetration depth and new imaging ability. Herein, high NIR-II-absorbing polymer particles were prepared by using soluble isobutyl-substituted diammonium borates (P-IDI). The P-IDI showed stronger absorption at 1000-1100 nm, which exhibited excellent photostability, strong photoacoustic imaging ability and high photothermal conversion efficiency (34.7%). The investigations in vitro and in vivo demonstrated that the excellent photothermal effect facilitated complete tumor ablation and also triggered immunogenic cell death in activation of the immune response. The high solubility and excellent photothermal conversion ability demonstrated that polymer IDI particles were promising theranostic agents for treatment of tumors with minor side effects.

Nomogram for predicting fulminant necrotizing enterocolitis.

BACKGROUND: Fulminant necrotizing enterocolitis (FNEC) is the most serious subtype of NEC and has a high mortality rate and a high incidence of sequelae. Onset prediction can help in the establishment of a customized treatment strategy. This study aimed to develop and evaluate a predictive nomogram for FNEC. METHODS: We conducted a retrospective observation to study the clinical data of neonates diagnosed with NEC (Bell stage ≥ IIB). Neonates were divided into the FNEC and NEC groups. A multivariate logistic regression model was used to construct the nomogram model. The performance of the nomogram was assessed using area under the curve, calibration analysis, and decision curve analysis. RESULTS: A total of 206 neonate cases were included, among which 40 (19.4%) fulfilled the definition of FNEC. The identified predictors were assisted ventilation after NEC onset; shock at NEC onset; feeding volumes before NEC onset; neutrophil counts on the day of NEC onset; and neutrophil, lymphocyte, and monocyte counts on day 1 after NEC onset. The nomogram exhibited good discrimination, with an area under the receiver operating characteristic curve of 0.884 (95% CI 0.825-0.943). The predictive model was well calibrated. Decision curve analysis confirmed the clinical usefulness of this nomogram. CONCLUSION: A nomogram with a potentially effective application was developed to facilitate the individualized prediction of FNEC, with the hope of providing further direction for the early diagnosis of FNEC and timing of intervention.

Multiple amino acid supplementations to reduce dietary protein for pigs during early and late finisher periods under commercial conditions.

BACKGROUND: With the easy availability and competitive prices of crystalline amino acids (AAs), the reduction of dietary crude protein (CP) for pigs during early and late finisher periods is possible under commercial conditions. Two experiments were conducted to assess the growth efficiency of early and late-finishing pigs fed with protein-restricted diets supplemented with Lys, Met, Thr, Trp, Val, Ile and His. In Experiment 1, 840 early finishing pigs were allocated to four dietary treatments with CP levels designed at 150, 142, 134, and 126 g kg-1 diet. In Experiment 2, 768 late-finishing pigs were allotted to four dietary treatments providing CP levels at 140, 130, 120, and 110 g kg-1 diet. RESULTS: In Experiment 1, the data showed that CP levels could be decreased from 150 to 126 g kg-1 without adversely affecting performance of early finishing pigs as no significant difference was observed for final bodyweight, average daily gain (ADG), feed to gain ratio (F:G), or average daily feed intake (ADFI). In Experiment 2, late-finishing pigs consuming 120 g kg-1 CP tended to have the highest ADG and lowest F:G whereas those fed the 110 g kg-1 CP diet showed the opposite trend. Based on quadratic analysis, the optimum CP levels to maximize ADG and minimize F:G were 126 and 127 g kg-1 , respectively. CONCLUSION: These findings showed that dietary CP levels could be decreased to 126 g kg-1 for early finishing pigs while improved performance was noted in late-finishing pigs consuming 120 g kg-1 CP. © 2023 Society of Chemical Industry.