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Purpose: We sought to develop an effective combined model for predicting the survival of patients with diffuse large B-cell lymphoma (DLBCL) based on the multimodal PET-CT deep features radiomics signature (DFR-signature)., Methods: 369 DLBCL patients from two medical centers were included in this study. Their PET and CT images were fused to construct the multimodal PET-CT images using a deep learning fusion network. Then the deep features were extracted from those fused PET-CT images, and the DFR-signature was constructed through an Automated machine learning (AutoML) model. Combined with clinical indexes from the Cox regression analysis, we constructed a combined model to predict the progression-free survival (PFS) and the overall survival (OS) of patients. In addition, the combined model was evaluated in the concordance index (C-index) and the time-dependent area under the ROC curve (tdAUC)., Results: A total of 1000 deep features were extracted to build a DFR-signature. Besides the DFR-signature, the combined model integrating metabolic and clinical factors performed best in terms of PFS and OS. For PFS, the C-indices are 0.784 and 0.739 in the training cohort and internal validation cohort, respectively. For OS, the C-indices are 0.831 and 0.782 in the training cohort and internal validation cohort., Conclusions: DFR-signature constructed from multimodal images improved the classification accuracy of prognosis for DLBCL patients. Moreover, the constructed DFR-signature combined with NCCN-IPI exhibited excellent potential for risk stratification of DLBCL patients., (© 2024. The Author(s).)

Porcine reproductive and respiratory syndrome (PRRS), caused by PRRS virus (PRRSV) infection, has been a serious threat to the pork industry worldwide and continues to bring significant economic loss. Current vaccination strategies offer limited protection against PRRSV transmission, highlighting the urgent need for novel antiviral approaches. In the present study, we reported for the first time that betulonic acid (BA), a widely available pentacyclic triterpenoids throughout the plant kingdom, exhibited potent inhibition on PRRSV infections in both Marc-145 cells and primary porcine alveolar macrophages (PAMs), with IC 50 values ranging from 3.3 µM to 3.7 µM against three different type-2 PRRSV strains. Mechanistically, we showed that PRRSV replication relies on energy supply from cellular ATP production, and BA inhibits PRRSV infection by reducing cellular ATP production. Our findings indicate that controlling host ATP production could be a potential strategy to combat PRRSV infections, and that BA might be a promising therapeutic agent against PRRSV epidemics.

Scenting is an important process for the formation of aroma quality in floral Longjing tea. There are differences in the aroma quality of osmanthus Longjing teas processed by different scenting processes. The efficient isolated scenting method was employed to process a new product of osmanthus Longjing tea in this study, and this was compared with the traditional scenting method. The volatile compounds of osmanthus Longjing tea were analyzed by a GC-MS instrument. In addition, the effects of scenting time and osmanthus consumption on the aroma quality of Longjing tea were studied. The results indicated that there were 67 kinds of volatile compounds in the osmanthus Longjing tea produced by the isolated scenting process (O-ISP), osmanthus Longjing tea produced by the traditional scenting process (O-TSP), and raw Longjing tea embryo (R), including alcohols, ketones, esters, aldehydes, olefins, acids, furans, and other aroma compounds. The proportions of alcohol compounds, ester compounds, aldehyde compounds, and ketone compounds in O-ISP were higher than in O-TSP and R. When the osmanthus consumption was increased, the relative contents of volatile aroma compounds gradually increased, which included the contents of trans-3,7-linalool oxide II, dehydrolinalool, linalool oxide III (furan type), linalool oxide IV (furan type), 2,6-Dimethyl cyclohexanol, isophytol, geraniol, 1-octene-3-alcohol, cis-2-pentenol, trans-3-hexenol, β-violet alcohol, 1-pentanol, benzyl alcohol, trans-p-2-menthene-1-alcohol, nerol, hexanol, terpineol, 6-epoxy-β-ionone, 4,2-butanone, 2,3-octanedione, methyl stearate, cis-3-hexenyl wasobutyrate, and dihydroanemone lactone. When the scenting time was increased, the relative contents of aroma compounds gradually increased, which included the contents of 2-phenylethanol, trans-3,7-linalool oxide I, trans-3,7-linalool oxide II, dehydrolinalool, isophytol, geraniol, trans-3-hexenol, β-ionol, benzyl alcohol, trans-p-2-menthene-1-ol, nerol, hexanol, terpineol, dihydroβ-ionone, α-ionone, and β-ionone,6,10. The isolated scenting process could achieve better aroma quality in terms of the floral fragrance, refreshing fragrance, and tender fragrance than the traditional scenting process. The isolated scenting process was suitable for processing osmanthus Longjing tea with high aroma quality. This study was hoped to provide a theoretical base for the formation mechanism and control of quality of osmanthus Longjing tea.

Accurate non-invasive monitoring of blood glucose (BG) is a challenging issue in the therapy of diabetes. Here near-infrared (NIR) photoplethysmography (PPG) sensor based on a vapor-deposited mixed tin-lead hybrid perovskite photodetector is developed. The device shows a high detectivity of 5.32 × 10 12 Jones and a large linear dynamic range (LDR) of 204 dB under NIR light, guaranteeing accurate extraction of eleven features from the PPG signal. By a combination of machine learning, accurate prediction of blood glucose level with mean absolute relative difference (MARD) as small as 2.48% is realized. The self-powered PPG sensor also works for real-time outdoor healthcare monitors using sunlight as a light source. The potential for early diabetes diagnoses by the perovskite PPG sensor is demonstrated., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Efficient treatment and utilization of organic pollutants in water are difficult for environmental remediation. A new hyper-cross-linked polymer (PIn-HCP) with high specific surface area was constructed via polyindole (PIn) as building blocks. Rich pore structures and abundant adsorption sites in PIn-HCP were obtained by hyper-cross-linking. The specific surface area of PIn-HCP was enhanced from 14.85 to 431.89 m 2 /g. The adsorption capacities of PIn-HCP-2 for methylene blue (MB), methyl orange (MO), rhodamine B (RhB), and tetracycline hydrochloride (TH) are 902.0, 275.2, 16.0, and 0.0 mg/g, respectively. PIn-HCP also realized selective adsorption of MB, which can better separate MB/RhB and MB/TH. MB is adsorbed onto PIn-HCP via a synergistic mechanism including π-π stacking, electrostatic interaction, cation-π interaction, hydrogen bonding interaction, and ion exchange. The huge conjugated structure of PIn promotes PIn-HCP to selectively adsorb MB. In addition, PIn-HCP also retains the electrochemical properties of PIn. MB can improve the specific capacitance of PIn-HCP up to five times, and it has potential as a supercapacitor electrode. PIn-HCP offers a promising and practical solution for the efficient treatment and utilization of organic pollutants in water.

Diagnostic pathology, historically dependent on visual scrutiny by experts, is essential for disease detection. Advances in digital pathology and developments in computer vision technology have led to the application of artificial intelligence (AI) in this field. Despite these advancements, the variability in pathologists' subjective interpretations of diagnostic criteria can lead to inconsistent outcomes. To meet the need for precision in cancer therapies, there is an increasing demand for accurate pathological diagnoses. Consequently, traditional diagnostic pathology is evolving towards "next-generation diagnostic pathology", prioritizing on the development of a multi-dimensional, intelligent diagnostic approach. Using nonlinear optical effects arising from the interaction of light with biological tissues, multiphoton microscopy (MPM) enables high-resolution label-free imaging of multiple intrinsic components across various human pathological tissues. AI-empowered MPM further improves the accuracy and efficiency of diagnosis, holding promise for providing auxiliary pathology diagnostic methods based on multiphoton diagnostic criteria. In this review, we systematically outline the applications of MPM in pathological diagnosis across various human diseases, and summarize common multiphoton diagnostic features. Moreover, we examine the significant role of AI in enhancing multiphoton pathological diagnosis, including aspects such as image preprocessing, refined differential diagnosis, and the prognostication of outcomes. We also discuss the challenges and perspectives faced by the integration of MPM and AI, encompassing equipment, datasets, analytical models, and integration into the existing clinical pathways. Finally, the review explores the synergy between AI and label-free MPM to forge novel diagnostic frameworks, aiming to accelerate the adoption and implementation of intelligent multiphoton pathology systems in clinical settings., (© 2024. The Author(s).)

African swine fever (ASF), caused by ASF virus (ASFV), represents one of the most economically important viral infectious diseases in swine industry worldwide. So far there is no vaccine or antiviral drug for controlling ASF pandemics. In the present study, we assessed inhibition of six nucleoside analogues against ASFV replication in ex vivo primary porcine alveolar macrophages (PAMs), including the first approved antiviral drug idoxuridine. Our results showed that, out of the assessed six compounds, 5-Bromo-2'-Deoxyuridine (5-BrdU, an analog of idoxuridine), exhibited the strongest inhibition on the replication of ASFV in PAMs with a 50% inhibitory concentration (IC 50 ) value of 2.9 μM and a low cytotoxicity (CC 50  > 270 μM). Moreover, we showed that 5-BrdU interferes with ASFV DNA replication by incorporating into viral replicating DNA molecules as a competitive substrate for deoxythymidine, ultimately inhibiting the formation of ASFV viral factories. Altogether, our findings suggest that 5-BrdU could serve as a promising therapeutic agent for combating ASFV infection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The continuous production of mature blood cell lineages is maintained by hematopoietic stem cells but they are highly susceptible to damage by ionizing radiation (IR) that induces death. Thus, devising therapeutic strategies that can mitigate hematopoietic toxicity caused by IR would benefit acute radiation syndrome (ARS) victims and patients receiving radiotherapy. Herein, we describe the preparation of an injectable hydrogel formulation based on Arg-Gly-Asp-alginate (RGD-Alg) and Laponite using a simple mixing method that ensured a slow and sustained release of interleukin-12 (IL-12) (RGD-Alg/Laponite@IL-12). The local administration of RGD-Alg/Laponite@IL-12 increased survival rates and promoted the hematopoietic recovery of mice who had received sublethal-dose irradiation. Local intra-bone marrow (intra-BM) injection of RGD-Alg/Laponite@IL-12 hydrogel effectively stimulated IL12 receptor-phosphoinositide 3-kinase/protein kinase B (IL-12R-PI3K/AKT) signaling axis, which promoted proliferation and hematopoietic growth factors secretion of BM mesenchymal stem/stromal cells. This signaling axis facilitates the repair of the hematopoietic microenvironment and plays a pivotal role in hematopoietic reconstitution. In conclusion, we describe a biomaterial-sustained release of IL-12 for the treatment of irradiated hematopoietic injury and provide a new therapeutic strategy for hematopoietic ARS., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Objective: Investigating the interaction between Mast cells (MCs) and Mononuclear Phagocytes (MPs) in the tumor microenvironment (TME) of blader cancer (BCa) to uncover potential immunotherapeutic targets. Methods: Single-cell RNA sequencing (scRNA-Seq) was conducted on 12 BCa patients to identify distinct subgroups of MCs and MPs. Transcriptome data was analyzed to characterize the phenotype, gene enrichment, cell-cell communication, and biological processes. The expression levels of cytokines were assessed by enzyme-linked immunosorbent assay (ELISA), while the chemotactic effects of cytokines were evaluated through Transwell assay. Results: In muscle-invasive bladder cancer (MIBC), the proportion of interferon-stimulated MC subtype (Mast-ISG15) increased. Mast-IL13 subgroup and Mast-CCL2 subgroups were functionally enriched in interferon (IFN) and nuclear factor kappa-B (NF-κB) signaling pathways. The Mast-CCL2 subgroup overexpressed the CCL2 gene, which could chemoattract MPs through CCL2. In vitro experiments confirmed that under stimulation, activated MCs activated IFN and NF-κB signaling, increasing the secretion of CCL2 and IL-13, chemoattracted THP-1 monocyte. Conclusion: This study revealed the vital role of MCs in shaping the TME of BCa. And provides new insights for the precise treatment of BCa., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Members of the genus Shewanella are known for their versatile electron accepting routes, which allow them to couple decomposition of organic matter to reduction of various terminal electron acceptors for heterotrophic growth in diverse environments. Here, we report autotrophic growth of Shewanella oneidensis MR-1 with photoelectrons provided by illuminated biogenic CdS nanoparticles. This hybrid system enables photosynthetic oscillatory acetate production from CO2 for over five months, far exceeding other inorganic-biological hybrid system that can only sustain for hours or days. Biochemical, electrochemical and transcriptomic analyses reveal that the efficient electron uptake of S. oneidensis MR-1 from illuminated CdS nanoparticles supplies sufficient energy to stimulate the previously overlooked reductive glycine pathway for CO2 fixation. The continuous solar-to-chemical conversion is achieved by photon induced electric recycling in sulfur species. Overall, our findings demonstrate that this mineral-assisted photosynthesis, as a widely existing and unique model of light energy conversion, could support the sustained photoautotrophic growth of non-photosynthetic microorganisms in nutrient-lean environments and mediate the reversal of coupled carbon and sulfur cycling, consequently resulting in previously unknown environmental effects. In addition, the hybrid system provides a sustainable and flexible platform to develop a variety of solar products for carbon neutrality., (© 2024 Wiley‐VCH GmbH.)

The new genus, Cerogamasus gen. nov., with the type species Cerogamasus tibetensis sp. nov., is established. The new genus is easily distinguished from other genera of Parasitidae because the dorsal idiosoma in both sexes bears more than 40 pairs of setae, of which fewer than 7 pairs of podonotal setae are smooth; the seta z5 of the dorsal hexagon is similar to j5 and j6 in form (pilose or distally pilose) while different in length ( z5 longer); the seta al of the palpfemur is pectinate, and al1 and al2 of the palpgenu are entire; the gnathotectum is trispinate; peritrematal shields in females are posteriorly free; and the palptrochanter in males has a pointed ventral protuberance. C. anhuiensis sp. nov., C. guizhouensis sp. nov. and C. multidentatus sp. nov. are described based on adult samples; C. tibetensis sp. nov. is described based on deutonymph and adult samples. Cycetogamasus coreanus Athias-Henriot, 1980, is transferred to Cerogamasus gen. nov. as a new combination.

In the exploitation of seawater resources, the transported pipelines are frequently corroded, resulting in economic losses and environmental pollution. The development of corrosion inhibitors is an effective measure to mitigate the corrosion of metals in seawater. In this work, novel chitosan oligosaccharide derivatives (CF) were synthesized as fluorescent eco-friendly corrosion inhibitor by modifying fluorescent monomers. The characterization of CF revealed excellent fluorescence intensity, promising the potential for on-line detection. The inhibition performance of CF on P110 in 3.5 wt% NaCl solution was investigated through experimental evaluation and theoretical analysis. The electrochemical measurements indicated that the corrosion inhibition efficiency was increased from 61.00 % to 91.19 % with the introduction of fluorane. Adsorption isotherm and XPS analysis demonstrated that CF is designed to protect metal by forming the composite film on P110 through physical and chemical adsorption. In addition, theoretical calculations revealed differences in the interaction energies, radial distribution functions and diffusion coefficients of inhibitors on the Fe (110) surface. These theoretical results aligned with the experiments and confirmed the excellent ability of CF in metal corrosion protection from the molecular perspective. This new chitosan derivative provides new possibilities for the development of the green composite inhibitor that allows on-line detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Systematic characterization of biological effects to genetic perturbation is essential to the application of molecular biology and biomedicine. However, the experimental exhaustion of genetic perturbations on the genome-wide scale is challenging. Here, we show TranscriptionNet, a deep learning model that integrates multiple biological networks to systematically predict transcriptional profiles to three types of genetic perturbations based on transcriptional profiles induced by genetic perturbations in the L1000 project: RNA interference, clustered regularly interspaced short palindromic repeat, and overexpression. TranscriptionNet performs better than existing approaches in predicting inducible gene expression changes for all three types of genetic perturbations. TranscriptionNet can predict transcriptional profiles for all genes in existing biological networks and increases perturbational gene expression changes for each type of genetic perturbation from a few thousand to 26 945 genes. TranscriptionNet demonstrates strong generalization ability when comparing predicted and true gene expression changes on different external tasks. Overall, TranscriptionNet can systemically predict transcriptional consequences induced by perturbing genes on a genome-wide scale and thus holds promise to systemically detect gene function and enhance drug development and target discovery., (© The Author(s) 2024. Published by Oxford University Press.)

Endometrial cancer is the most common gynecological cancer in the developed world. However, the accuracy of current diagnostic methods is still unsatisfactory and time-consuming. Here, we presented an alternate approach to monitoring the progression of endometrial cancer via multiphoton microscopy imaging and analysis of collagen, which is often overlooked in current endometrial cancer diagnosis protocols but can offer a crucial signature in cancer biology. Multiphoton microscopy (MPM) based on the second-harmonic generation and two-photon excited fluorescence was introduced to visualize the microenvironment of endometrium in normal, hyperplasia without atypia, atypical hyperplasia, and endometrial cancer specimens. Furthermore, automatic image analysis based on the MPM image processing algorithm was used to quantify the differences in the collagen morphological features among them. MPM enables the visualization of the morphological details and alterations of the glands in the development process of endometrial cancer, including irregular changes in the structure of the gland, increased ratio of the gland to the interstitium, and atypical changes in the glandular epithelial cells. Moreover, the destructed basement membrane caused by gland proliferation and fusion is clearly shown in SHG images, which is a key feature for identifying endometrial cancer progression. Quantitative analysis reveals that the formation of endometrial cancer is accompanied by an increase in collagen fiber length and width, a progressive linearization and loosening of interstitial collagen, and a more random arrangement of interstitial collagen. Observation and quantitative analysis of interstitial collagen provide invaluable information in monitoring the progression of endometrial cancer. Label-free multiphoton imaging reported here has the potential to become an in situ histological tool for effective and accurate early diagnosis and detection of malignant lesions in endometrial cancer., (© 2024. The Author(s).)

In military and aerospace fields, petrol and aviation kerosene are the preferred fuels for micro power systems due to their reduced carrying load and convenient fuel source. Therefore, n-heptane, an alternative to petrol and aviation paraffin, was chosen as the fuel. A micro quartz glass tube was used as the combustor, and the premixed combustion characteristics of n-heptane/air were investigated using numerical simulations. The method used to improve the internal flow channel includes a built-in cross baffle and scaled backward-facing step. The resulting optimized combustion characteristics, such as internal flow line, wall temperature, CO emission, and wall radiation, have been analyzed. The results indicate that, with a fixed equivalence ratio of 1.0 and a n-heptane mass flow rate of 2.70 mg/s, the built-in cross baffle concentrates and stabilizes the high temperature zone of the flame, resulting in a significant increase in wall temperature. Conversely, the use of the micro tube with scaled backward-facing step creates a reflux zone due to the sudden expansion of the inlet cross-section, which promotes better fuel mixing and flame anchoring. Furthermore, after comparing the output efficiencies of micro tube with different internal structures, it was discovered that enhancing the internal channel of the micro tube is crucial for increasing the wall radiation efficiency., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

After long-term clinical application, traditional Chinese medicine (TCM) has accumulated rich experience in the stroke treatment. Huang-Qi-Long-Dan Granule (HQLDG) is a TCM formula that has been used in clinical for the treatment of acute ischemic stroke. However, its mechanism against ischemic stroke is still unknown. This study aimed to identify HQLDG's effect against ischemic stroke and explore its underlying mechanism. 16s rRNA sequencing, metabolomics/tryptophan (Trp)-targeted metabolomics analysis and transcriptomic analysis were used to investigate HQLDG underlying therapeutic mechanism. Our results revealed that HQLDG significantly decreased the infarct volume, improved mouse behavior and brain slices pathological staining. In addition, it could ameliorate intestinal barrier damage and regulate tight junction gene expression. 16s rRNA, metabolomics and transcriptomics analysis revealed that HQLDG treatment significantly improved the composition of gut microbiota and Trp metabolism pathway, and further downregulated Th17/IL-17 signaling pathway. HQLDG treatment could significantly decrease serum inflammatory cytokines, IL-17A and IL-22; down-regulate Trp metabolism receptor gene (Ahr), inflammatory cytokines genes (IL-17a, IL-22), and an important coding gene for maintaining the mature Th17 (rorc) in both brain and intestinal tissues. In the contrary, after gut microbiota removal, this effect of HQLDG was impaired. HQLDG treated mouse fecal microbiota transplantation also had positive effect against tMCAO injury. Moreover, AhR inhibitor could decrease IL-17A immunofluorescence. These results suggested that the gut microbiota regulation might be an important intermediate in HQLDG against tMCAO injury. HQLDG might exert anti-ischemic stroke effects through the gut microbiota-Trp metabolism-Th17/IL-17 signaling, which provides new insights into HQLDG-mediated prevention in ischemic stroke., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

African swine fever (ASF), caused by the African swine fever virus (ASFV), is one of the most important infectious diseases that cause high morbidity and mortality in pigs and substantial economic losses to the pork industry of affected countries due to the lack of effective vaccines. The need to develop alternative robust antiviral countermeasures, especially anti-ASFV agents, is of the utmost urgency. This study shows that fangchinoline (FAN), a bisbenzylisoquinoline alkaloid found in the roots of Stephania tetrandra of the family Menispermaceae, significantly inhibits ASFV replication in porcine alveolar macrophages (PAMs) at micromolar concentrations (IC 50 = 1.66 µM). Mechanistically, the infection of ASFV triggers the AKT/mTOR/NF-κB signaling pathway. FAN significantly inhibits ASFV-induced activation of such pathways, thereby suppressing viral replication. Such a mechanism was confirmed using an AKT inhibitor MK2206 as it inhibited AKT phosphorylation and ASFV replication in PAMs. Altogether, the results suggest that the AKT/mTOR pathway could potentially serve as a treatment strategy for combating ASFV infection and that FAN could potentially emerge as an effective novel antiviral agent against ASFV infections and deserves further in vivo antiviral evaluations.

Objectives: This study aims to develop 7×7 machine-learning cross-combinatorial methods for selecting and classifying radiomic features used to construct Radiomics Score (RadScore) of predicting the mid-term efficacy and prognosis in high-risk patients with diffuse large B-cell lymphoma (DLBCL)., Methods: Retrospectively, we recruited 177 high-risk DLBCL patients from two medical centers between October 2012 and September 2022 and randomly divided them into a training cohort (n=123) and a validation cohort (n=54). We finally extracted 110 radiomic features along with SUVmax, MTV, and TLG from the baseline PET. The 49 features selection-classification pairs were used to obtain the optimal LASSO-LASSO model with 11 key radiomic features for RadScore. Logistic regression was employed to identify independent RadScore, clinical and PET factors. These models were evaluated using receiver operating characteristic (ROC) curves and calibration curves. Decision curve analysis (DCA) was conducted to assess the predictive power of the models. The prognostic power of RadScore was assessed using cox regression (COX) and Kaplan-Meier plots (KM)., Results: 177 patients (mean age, 63 ± 13 years,129 men) were evaluated. Multivariate analyses showed that gender (OR,2.760; 95%CI:1.196,6.368); p =0.017), B symptoms (OR,4.065; 95%CI:1.837,8.955; p =0.001), SUVmax (OR,2.619; 95%CI:1.107,6.194; p =0.028), and RadScore (OR,7.167; 95%CI:2.815,18.248; p <0.001) independently contributed to the risk factors for predicting mid-term outcome. The AUC values of the combined models in the training and validation groups were 0.846 and 0.724 respectively, outperformed the clinical model (0.714;0.556), PET based model (0.664; 0.589), NCCN-IPI model (0.523;0.406) and IPI model (0.510;0.412) in predicting mid-term treatment outcome. DCA showed that the combined model incorporating RadScore, clinical risk factors, and PET metabolic metrics has optimal net clinical benefit. COX indicated that the high RadScore group had worse prognosis and survival in progression-free survival (PFS) (HR, 2.1737,95%CI: 1.2983, 3.6392) and overall survival (OS) (HR,2.1356,95%CI: 1.2561, 3.6309) compared to the low RadScore group. KM survival analysis also showed the same prognosis prediction as Cox results., Conclusion: The combined model incorporating RadScore, sex, B symptoms and SUVmax demonstrates a significant enhancement in predicting medium-term efficacy and prognosis in high-risk DLBCL patients. RadScore using 7×7 machine learning cross-combinatorial methods for selection and classification holds promise as a potential method for evaluating medium-term treatment outcome and prognosis in high-risk DLBCL patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Rong, Zhao, Teng, Jiang, Chen and Xu.)

This study was designed to discern the effect of heavy scavenger metallothionein on glutathione (GSH) deprivation-evoked cardiac anomalies and mechanisms involved with an emphasis on ferroptosis. Wild-type and cardiac metallothionein transgenic mice received GSH synthase inhibitor buthionine sulfoximine (BSO; 30 mmol/L in drinking water) for 14 days before assessment of myocardial morphology and function. BSO evoked cardiac remodeling and contractile anomalies, including cardiac hypertrophy, interstitial fibrosis, enlarged left ventricular chambers, deranged ejection fraction, fraction shortening, cardiomyocyte contractile capacity, intracellular Ca 2+ handling, sarcoplasmic reticulum Ca 2+ reuptake, loss of mitochondrial integrity (mitochondrial swelling, loss of aconitase activity), mitochondrial energy deficit, carbonyl damage, lipid peroxidation, ferroptosis, and apoptosis. Metallothionein itself did not affect myocardial morphology and function, although it mitigated BSO-provoked myocardial anomalies, loss of mitochondrial integrity and energy, and ferroptosis. Immunoblotting revealed down-regulated sarco(endo)plasmic reticulum Ca 2+ -ATPase 2a, glutathione peroxidase 4, ferroptosis-suppressing CDGSH iron-sulfur domain 1 (CISD1), and mitochondrial regulating glycogen synthase kinase-3β phosphorylation with elevated p53, myosin heavy chain-β isozyme, IκB phosphorylation, and solute carrier family 7 member 11 (SLC7A11) as well as unchanged SLC39A1, SLC1A5, and ferroptosis-suppressing protein 1 following BSO challenge, all of which, except glutamine transporter SLC7A11 and p53, were abrogated by metallothionein. Inhibition of CISD1 using pioglitazone nullified GSH-offered benefit against BSO-induced cardiomyocyte ferroptosis and contractile and intracellular Ca 2+ derangement. Taken together, these findings support a regulatory modality for CISD1 in the impedance of ferroptosis in metallothionein-offered protection against GSH depletion-evoked cardiac aberration., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Pancreatic ductal adenocarcinoma (PDAC) ranks among the deadliest types of cancer, and it will be meaningful to search for new biomarkers with prognostic value to help clinicians tailor therapeutic strategies., Methods: Here we tried to use an advanced optical imaging technique, multiphoton microscopy (MPM) combining second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF) imaging, for the label-free detection of PDAC tissues from a cohort of 149 patients. An automated image processing method was used to extract collagen features from SHG images and the Kaplan-Meier survival analysis and Cox proportional hazards regression were used to assess the prognostic value of collagen signatures., Results: SHG images clearly show the different characteristics of collagen fibers in tumor microenvironment. We gained eight collagen morphological features, and a Feature-score was derived for each patient by the combination of these features using ridge regression. Statistical analyses reveal that Feature-score is an independent factor, and can predict the overall survival of PDAC patients as well as provide well risk stratification., Conclusions: SHG imaging technique can potentially be a tool for the accurate diagnosis of PDAC, and this optical biomarker (Feature-score) may help clinicians make more approximate treatment decisions., (© 2024. The Author(s).)

In this study, we outline a general method for the construction of various (furyl)methyl disulfides from acetyl-masked disulfide nucleophiles and ene-yne-ketones. This protocol is feathered by metal-free, simple experimental conditions, high efficiency, and scalable potential, which make it attractive and practical.

Ductal carcinoma in situ with microinvasion (DCISM) is a challenging subtype of breast cancer with controversial invasiveness and prognosis. Accurate diagnosis of DCISM from ductal carcinoma in situ (DCIS) is crucial for optimal treatment and improved clinical outcomes. However, there are often some suspicious small cancer nests in DCIS, and it is difficult to diagnose the presence of intact myoepithelium by conventional hematoxylin and eosin (H&E) stained images. Although a variety of biomarkers are available for immunohistochemical (IHC) staining of myoepithelial cells, no single biomarker is consistently sensitive to all tumor lesions. Here, we introduced a new diagnostic method that provides rapid and accurate diagnosis of DCISM using multiphoton microscopy (MPM). Suspicious foci in H&E-stained images were labeled as regions of interest (ROIs), and the nuclei within these ROIs were segmented using a deep learning model. MPM was used to capture images of the ROIs in H&E-stained sections. The intensity of two-photon excitation fluorescence (TPEF) in the myoepithelium was significantly different from that in tumor parenchyma and tumor stroma. Through the use of MPM, the myoepithelium and basement membrane can be easily observed via TPEF and second-harmonic generation (SHG), respectively. By fusing the nuclei in H&E-stained images with MPM images, DCISM can be differentiated from suspicious small cancer clusters in DCIS. The proposed method demonstrated good consistency with the cytokeratin 5/6 (CK5/6) myoepithelial staining method (kappa coefficient = 0.818)., (© 2024 UICC.)

African swine fever (ASF) caused by African swine fever virus (ASFV) is a highly infectious and lethal swine disease. Currently, there is only one novel approved vaccine and no antiviral drugs for ASFV. In the study, a high-throughput screening of an FDA-approved drug library was performed to identify several drugs against ASFV infection in primary porcine alveolar macrophages. Triapine and cytarabine hydrochloride were identified as ASFV infection inhibitors in a dose-dependent manner. The two drugs executed their antiviral activity during the replication stage of ASFV. Furthermore, molecular docking studies showed that triapine might interact with the active center Fe 2+ in the small subunit of ASFV ribonucleotide reductase while cytarabine hydrochloride metabolite might interact with three residues (Arg589, Lys593, and Lys631) of ASFV DNA polymerase to block new DNA chain extension. Taken together, our results suggest that triapine and cytarabine hydrochloride displayed significant antiviral activity against ASFV in vitro., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Ischemic stroke frequently leads to a condition known as post-stroke cognitive impairment (PSCI). Timely recognition of individuals susceptible to developing PSCI could facilitate the implementation of personalized strategies to mitigate cognitive deterioration. High mobility group box 1 (HMGB1) is a protein released by ischemic neurons and implicated in inflammation after stroke. Circulating levels of HMGB1 could potentially serve as a prognostic indicator for the onset of cognitive impairment following ischemic stroke., Objective: To investigate the predictive value of circulating HMGB1 concentrations in the acute phase of ischemic stroke for the development of cognitive dysfunction at the 3-month follow-up., Methods: A total of 192 individuals experiencing their initial episode of acute cerebral infarction were prospectively recruited for this longitudinal investigation. Concentrations of circulating HMGB1 were quantified using an enzyme-linked immunosorbent assay (ELISA) technique within the first 24 hours following hospital admission. Patients underwent neurological evaluation including NIHSS scoring. Neuropsychological evaluation was conducted at the 3-month follow-up after the cerebrovascular event, employing the Montreal Cognitive Assessment (MoCA) as the primary tool for assessing cognitive performance. Multivariable logistic regression models were employed to investigate the relationship between circulating HMGB1 concentrations and cognitive dysfunction following stroke, which was operationalized as a MoCA score below 26, while controlling for potential confounders including demographic characteristics, stroke severity, vascular risk factors, and laboratory parameters., Results: Of 192 patients, 84 (44%) developed PSCI. Circulating HMGB1 concentrations were significantly elevated in individuals who developed cognitive dysfunction following stroke compared to those who maintained cognitive integrity (8.4 ± 1.2 ng/mL vs 4.6 ± 0.5 ng/mL, respectively; p  < 0.001). The prevalence of PSCI showed a dose-dependent increase with higher HMGB1 quartiles. After controlling for potential confounders such as demographic factors (age, gender, and education), stroke severity, vascular risk factors, and laboratory parameters in a multivariable logistic regression model, circulating HMGB1 concentrations emerged as a significant independent predictor of cognitive dysfunction following stroke (regression coefficient = 0.236, p  < 0.001)., Conclusion: Circulating HMGB1 concentrations quantified within the first 24 hours following acute cerebral infarction are significantly and independently correlated with the likelihood of developing cognitive dysfunction at the 3-month follow-up, even after accounting for potential confounding factors. HMGB1 may be a novel biomarker to identify patients likely to develop post-stroke cognitive impairment for targeted preventive interventions., Competing Interests: The authors declare there are no competing interests., (©2024 Liu et al.)

Meningiomas rank among the most common intracranial tumors, and surgery stands as the primary treatment modality for meningiomas. The precise subtyping and diagnosis of meningiomas, both before and during surgery, play a pivotal role in enabling neurosurgeons choose the optimal surgical program. In this study, we utilized multiphoton microscopy (MPM) based on 2-photon excited fluorescence and second-harmonic generation to identify 5 common meningioma subtypes. The morphological features of these subtypes were depicted using the MPM multichannel mode. Additionally, we developed 2 distinct programs to quantify collagen content and blood vessel density. Furthermore, the lambda mode of the MPM characterized architectural and spectral features, from which 3 quantitative indicators were extracted. Moreover, we employed machine learning to differentiate meningioma subtypes automatically, achieving high classification accuracy. These findings demonstrate the potential of MPM as a noninvasive diagnostic tool for meningioma subtyping and diagnosis, offering improved accuracy and resolution compared with traditional methods., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Pancreatic intraepithelial neoplasia (PanIN) is the most common precursor lesion that has the potential to progress to invasive pancreatic cancer, and early and rapid detection may offer patients a chance for treatment before the development of invasive carcinoma. Therefore, the identification of PanIN holds significant clinical importance. In this study, we first used multiphoton microscopy (MPM) combining two-photon excitation fluorescence and second-harmonic generation imaging to label-free detect PanIN and attempted to differentiate between normal pancreatic ducts and different grades of PanIN. Then, we also developed an automatic image processing strategy to extract eight morphological features of collagen fibers from MPM images to quantify the changes in collagen fibers surrounding the ducts. Experimental results demonstrate that the combination of MPM and quantitative information can accurately identify normal pancreatic ducts and different grades of PanIN. This study may contribute to the rapid diagnosis of pancreatic diseases and may lay the foundation for further clinical application of MPM., (© 2024 Wiley‐VCH GmbH.)

Background: The histological grade is an important factor in the prognosis of invasive breast cancer and is vital to accurately identify the histological grade and reclassify of Grade2 status in breast cancer patients., Methods: In this study, data were collected from 556 invasive breast cancer patients, and then randomly divided into training cohort (n = 335) and validation cohort (n = 221). All patients were divided into actual low risk group (Grade1) and high risk group (Grade2/3) based on traditional histological grade, and tumor-infiltrating lymphocyte score (TILs-score) obtained from multiphoton images, and the TILs assessment method proposed by International Immuno-Oncology Biomarker Working Group (TILs-WG) were also used to differentiate between high risk group and low risk group of histological grade in patients with invasive breast cancer. Furthermore, TILs-score was used to reclassify Grade2 (G2) into G2 /Low risk and G2/High risk. The coefficients for each TILs in the training cohort were retrieved using ridge regression and TILs-score was created based on the coefficients of the three kinds of TILs., Results: Statistical analysis shows that TILs-score is significantly correlated with histological grade, and is an independent predictor of histological grade (odds ratio [OR], 2.548; 95%CI, 1.648-3.941; P < 0.0001), but TILs-WG is not an independent predictive factor for grade (P > 0.05 in the univariate analysis). Moreover, the risk of G2/High risk group is higher than that of G2/Low risk group, and the survival rate of patients with G2/Low risk is similar to that of Grade1, while the survival rate of patients with G2/High risk is even worse than that of patients with G3., Conclusion: Our results suggest that TILs-score can be used to predict the histological grade of breast cancer and potentially to guide the therapeutic management of breast cancer patients., (© 2024. The Author(s).)

Traditional pyrolysis biochar has been widely employed to treat dye wastewater. However, there are some problems in the pyrolysis process, such as the generation of harmful gases and the low content of silico-oxygen functional groups to promote adsorption. Straw biochar (Ac-BC bm ) was prepared by sulfuric acid co-ball milling method. The adsorption performance and adsorption mechanism of rhodamine B (RhB) under different preparation conditions and factors were investigated. The results showed that the adsorption rate of Ac-BC bm on RhB was up to 94.9%, which was 60.5% and 55.8% higher than that of ball-milling straw (ST bm ) and biochar prepared by pyrolysis (STBC600), respectively. The Ac-BC bm had better adaptability under different pH and common interfering ions for remove RhB. Characterization and DFT simulation analysis revealed that the sulfuric acid co-ball milling process promoted the formation of Si-OH and Si-O-CH 3 oxygen-containing functional groups of Si component in straw, which enhanced the hydrogen bonding interactions and effectively improved the adsorption efficiency. This study investigated a new strategy for biochar preparation by sulfuric acid co-ball milling, which provides an additional development direction for the efficient resource utilization of straw., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Thanks to the advancements in bioinformatics, drugs, and other interventions that modulate microbes to treat diseases have been emerging continuously. In recent years, an increasing number of databases related to traditional Chinese medicine (TCM) or gut microbes have been established. However, a database combining the two has not yet been developed. To accelerate TCM research and address the traditional medicine and micro ecological system connection between short board, we have developed the most comprehensive micro-ecological database of TCM. This initiative includes the standardization of the following advantages: (1) A repeatable process achieved through the standardization of a retrieval strategy to identify literature. This involved identifying 419 experiment articles from PubMed and six authoritative databases; (2) High-quality data integration achieved through double-entry extraction of literature, mitigating uncertainties associated with natural language extraction; (3) Implementation of a similar strategy aiding in the prediction of mechanisms of action. Leveraging drug similarity, target entity similarity, and known drug-target entity association, our platform enables the prediction of the effects of a new herb or acupoint formulas using the existing data. In total, MicrobeTCM includes 171 diseases, 725 microbes, 1468 herb-formulas, 1032 herbs, 15780 chemical compositions, 35 acupoint-formulas, and 77 acupoints. For further exploration, please visit https://www.microbetcm.com., Competing Interests: Declaration of Competing Interest We the undersigned declare that this manuscript entitled “MicrobeTCM: A comprehensive platform for the interactions of microbiota and traditional Chinese medicine”. Graphical Abstract was supported by Figdraw (ID:OTOOO89898). All authors disclosed no relevant relationships., (Copyright © 2024. Published by Elsevier Ltd.)

Under transition-metal-free conditions, trisulfide dioxides were used as disulfurating reagents to react with a wide range of amides, affording various substituted N -disulfanyl amides in good yields. Furthermore, the gram-scale experiment has confirmed the practicability of this approach.

The present study was conducted to characterize the clinicopathologic characteristics, immunohistochemical staining results, and immune checkpoint inhibitors (ICIs) efficacy in patients with SMARCA4-deficient/TP53 mutant lung cancer. Patients diagnosed with advanced or metastatic undifferentiated lung cancer harboring SMARCA4-deficient and TP53 mutations, however, without targetable sensitive mutations were retrieved from the electronic medical record system. Descriptive statistics were used to describe the baseline characteristics and clinical features including age, gender, eastern cooperative oncology group performance status, disease stage, smoking status, chief complaint, site of the primary mass, tumor size, gross type, symptoms, local invasion, and metastatic sizes. Immunological markers and potential drive genes were detected by immunohistochemical staining and next generation sequencing. Efficacy and safety profile of ICIs in included patients was evaluated with progression-free survival and overall survival. Between January 2019 and September 2022, there were 4 patients included within the inclusion criteria in the present study. Biomarkers including CK, CK7, and integrase interactor 1 were detected positive, however, other immunological markers including CK20, CD56, P63, P40, NapsinA, TTF-1, CgA, Syn, BRG1, or PD-L1 were detected negative among them. Results of next generation sequencing panel were failed to discover any targetable sensitive mutations. A total of 4 mutation types of TP53, including p.C141Y, p.S240G, p.E339X (terminator acquired), and p.L130F detected for the patients, respectively. Microsatellite stability status, as well as low tumor mutation burden was identified among all the patients. Median progression-free survival for ICIs as first line treatment and median overall survival were 3.25 months (range from 1.3 to 6.8 months), and 6.0 months (range from 2.7 to 9.6 months), respectively. Our results indicated that advanced lung cancer patients harboring co-occurring SMARCA4-deficient/TP53 mutations might respond to ICIs treatment, though within negative programmed cell death-ligand 1 expression or low tumor mutation burden. However, hyperprogressive disease by ICIs may also happen for such patients. The mutation types of TP53 might play a role during the exposure of ICIs, however, need further identification in basic experiments., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study aimed to investigate the associations between the clinical characteristics and effectiveness of anti-PD-1 inhibitors in patients with EGFR-sensitive mutations, aiming to identify the potential subgroup of patients who might benefit from anti-PD-1 inhibitor treatment. Patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)-sensitive mutations who received subsequent anti-PD-1 inhibitors in combination with chemotherapy/antiangiogenic agents or alone after progression to tyrosine kinase inhibitors (TKIs) were screened. Clinical characteristics, including hematological parameters, were investigated for potential correlations with clinical outcomes. Subgroup and multivariate analyses were used for further confirmation of the relationship. Kaplan-Meier curves and Cox survival regression models using the log-rank test were used for progression-free survival (PFS) and overall survival (OS) assessments between the groups. Multiple regression analysis was performed using the standard regression coefficient values. The Wilcoxon test was used for the analysis of the variation in NLR. P ≤ 0.05 was considered to indicate statistical significance. This study was a retrospective study. Twenty-two patients met the inclusion criteria and were included in the study. The median PFS was 3.05 months (95% CI, 2.9-10.2 months). The median OS was 7.30 months (95% CI, 5.2-18.1 months). PFS in low neutrophil to lymphocyte ratio (NLR ≤ 4) was significantly longer than high NLR (NLR > 4, 5.7 months versus 2.0 months, HR, 0.35, 95% CI, 0.08-0.63, P = 0.0083). The OS in the low NLR group was also significantly better than that in the high NLR group (OS, 21.3 months versus 5.0 months, HR, 0.33; 95% CI, 0.09-0.74; P = 0.0163). In the multivariate analysis, NLR was the only significant factor for OS benefits (β = 3.535, 95% CI, 1.175-10.636, P = 0.025). Further investigation revealed that front-line TKIs exposure may contribute to the elevation or decrease of NLR, and finally lead to different efficacy outcomes by anti-PD-1 inhibitors. The findings suggest that a portion of advanced NSCLC patients with low NLR characteristics (NLR ≤ 4), even those harboring EGFR-sensitive mutations, could benefit from anti-PD-1 inhibitors as further line treatment after progression to EGFR-TKIs., (© 2024. The Author(s).)

Eucalyptus cinerea is an evergreen tree in the Myrtaceae. It is native to southern and eastern New South Wales and northern and eastern Victoria, Australia. It was introduced into China in the 1980s (Silva et al. 2011). Because of its unique shape, flexible stems, and rapid growth characteristics, it is widely used in the pulp industry and in decorative materials such as flower bouquets. In July 2022, 5- to 10-year-old E. cinerea showing symptoms of dehydration, withering and yellowing leaves, were found in forests and nurseries in Kunming and Songming, China. More than 37% of the trees showed these symptoms at each location, and disease severity was about 30%. Sixty symptomatic plants were collected from five tree nurseries. Diseased roots with 2-cm-long lesions were soaked in 75% ethanol for 15 s, 0.1% mercuric chloride for 2 min, rinsed with sterilized water, and placed on potato dextrose agar (PDA) at 25℃ for 3 days. Thirty samples were plated, and 21 isolates (YJLGF01 to YJLGF21) obtained, 11 strains with similar colony morphology (including representative strains YJLGF03 to YJLGF05). Three isolates (YJLGF03 to YJLGF05) were obtained by single-spore purification. On PDA, the colonies were circular with fluffy white to light yellow mycelium; the underside was yellowish brown. Conidiophores were bifurcated, with macroconidia borne terminally. The macroconidia were cylindrical with rounded, blunt ends, yellow to transparent, 1 to 3 septate (22.5 to 47.6 × 4.5 to 7.1 µm); microconidia were 0 to 1 septate (12.5 to 19.6 × 4.7 to 6.4 µm). Chlamydospores were spherical, rosary-like, and light yellow. Morphological characteristics were consistent with published descriptions of Dactylonectria pauciseptata (Piperkova et al. 2017). For molecular identification, the internal transcribed spacer (ITS), translation elongation factor 1- alpha (ef1-α) gene, and the beta-tubulin 2 (β-tub2) gene were amplified and sequenced (ITS accessions OR735053, OR735054, OR735055; β-tub2 accessios OR757447, OR757448, OR757449; ef1-α accessions OR757450, OR757451, OR757451) using published primers (White et al. 1990; Carbone et al. 1999). A phylogenetic tree was developed by Maximum Parsimony (MP) and Maximum Likelihood (ML) methods. These three isolates fell into the D. pauciseptata clade and were distinguished clearly from other species. Pathogenicity tests were performed using the same three isolates. Each isolate was cultured on PDA, and then subcultured in V8 juice broth on an orbital shaker at 180 RPM for 5 days. Conidia were collected by centrifugation at 6,000 RPM for 5 min, and then resuspended in sterilized distilled water (1×106 conidia/ml). Injured roots of one-year-old E. cinerea were soaked in the spore suspension for 1 h before being transplanted in sterile vermiculite. The plants were incubated at 25℃ with a 12 h photoperiod and 90% humidity. Five plants were inoculated as a group for each treatment and the entire experiment was completed three times. Among the inoculated plants, the incidence of disease development was 100%. A small sot appeared after 4 days, with a water-soaked lesion appearing and gradually expanding during days 5 to 7. After 10 days symptoms of root necrosis were similar to the those observed in the nursery, and aboveground plant parts had yellow, withering leaves and defoliation after 10 to 15 days. Control plants treated with sterile water showed no disease symptoms. The three strains were successfully reisolated from inoculated seedlings and confirmed them using DNA sequencing. No isolates were obtained from the control plants, thus fulfilling Koch's postulates. Dactylonectria pauciseptata was first reported from necrotic tissue of infected grape roots (Schroers et al. 2008). So far, it has been reported in Turkey, Canada, Brazil, Italy, and other countries (Erper et al. 2013; Úrbez-Torres et al. 2014; Santos et al. 2014). Based on our results, E. cinerea is a new host plant of D. pauciseptata in China. This disease is a threat to the nursery production of E. cinerea, potentially leading to a reduction in yields and economic losses.

Our previous study revealed that green tea polysaccharide conjugate (gTPC) has emulsion effect, but its emulsifying ability is weak. In order to improve the emulsification ability of gTPC, gTPC and bovine serum albumin (BSA) were combined to form five different mass proportions of the TPC/BSA (TB) complex: TPC/BSA: 5:1, 5:2, 5:3, 5:4, and 5:5 w/w. We observed that the 5:5 w/w TB emulsion was more hydrophobic and surface-active. Furthermore, the emulsions prepared using 50.00 wt% medium-chain triglycerides exhibited the best stability. In addition, the TB emulsion exhibited stability in adverse environments of pH, salt, and heat; in particular, under salt conditions, no significant changes were observed in zeta potential. Subsequently, in vitro simulated digestion experiments were performed to investigate the use of TB emulsions for β-carotene encapsulation. We observed that the encapsulation efficiency for β-carotene was approximately 90.0 %; it was subsequently released in the intestine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Collagen features in breast tumor microenvironment is closely associated with the prognosis of patients. We aim to explore the prognostic significance of collagen features at breast tumor border by combining multiphoton imaging and imaging analysis., Methods: We used multiphoton microscopy (MPM) to label-freely image human breast tumor samples and then constructed an automatic classification model based on deep learning to identify collagen signatures from multiphoton images. We recognized three kinds of collagen signatures at tumor boundary (CSTB I-III) in a small-scale, and furthermore obtained a CSTB score for each patient based on the combined CSTB I-III by using the ridge regression analysis. The prognostic performance of CSTB score is assessed by the area under the receiver operating characteristic curve (AUC), Cox proportional hazard regression analysis, as well as Kaplan-Meier survival analysis., Results: As an independent prognostic factor, statistical results reveal that the prognostic performance of CSTB score is better than that of the clinical model combining three independent prognostic indicators, molecular subtype, tumor size, and lymph nodal metastasis (AUC, Training dataset: 0.773 vs. 0.749; External validation: 0.753 vs. 0.724; HR, Training dataset: 4.18 vs. 3.92; External validation: 4.98 vs. 4.16), and as an auxiliary indicator, it can greatly improve the accuracy of prognostic prediction. And furthermore, a nomogram combining the CSTB score with the clinical model is established for prognosis prediction and clinical decision making., Conclusion: This standardized and automated imaging prognosticator may convince pathologists to adopt it as a prognostic factor, thereby customizing more effective treatment plans for patients., (© 2023. Springer Nature Switzerland AG.)

Errors are common issues in quantum computing platforms, among which leakage is one of the most-challenging to address. This is because leakage, i.e., the loss of information stored in the computational subspace to undesired subspaces in a larger Hilbert space, is more difficult to detect and correct than errors that preserve the computational subspace. As a result, leakage presents a significant obstacle to the development of fault-tolerant quantum computation. In this paper, we propose an efficient and accurate benchmarking framework called leakage randomized benchmarking (LRB), for measuring leakage rates on multi-qubit quantum systems. Our approach is more insensitive to state preparation and measurement (SPAM) noise than existing leakage benchmarking protocols, requires fewer assumptions about the gate set itself, and can be used to benchmark multi-qubit leakages, which has not been achieved previously. We also extended the LRB protocol to an interleaved variant called interleaved LRB (iLRB), which can benchmark the average leakage rate of generic n -site quantum gates with reasonable noise assumptions. We demonstrate the iLRB protocol on benchmarking generic two-qubit gates realized using flux tuning and analyzed the behavior of iLRB under corresponding leakage models. Our numerical experiments showed good agreement with the theoretical estimations, indicating the feasibility of both the LRB and iLRB protocols.

A popular non-alcoholic beverage worldwide, tea can regulate blood glucose levels, lipid levels, and blood pressure, and may even prevent type 2 diabetes mellitus (T2DM). Different tea fermentation levels impact these effects. Tea products with different fermentation degrees containing different functional ingredients can lower post-meal blood glucose levels and may prevent T2DM. There are seven critical factors that shed light on how teas with different fermentation levels affect blood glucose regulation in humans. These factors include the inhibition of digestive enzymes, enhancement of cellular glucose uptake, suppression of gluconeogenesis-related enzymes, reduction in the formation of advanced glycation end products (AGEs), inhibition of dipeptidyl peptidase-4 (DPP-4) activity, modulation of gut flora, and the alleviation of inflammation associated with oxidative stress. Fermented teas can be used to lower post-meal blood glucose levels and can help consumers make more informed tea selections.

Sprouting is an irreversible deterioration of potato quality, which leads to the production of harmful toxins and loss of the commercial value of potatoes. However, there is no report on the changes in different stages of potato sprouting through transcriptome and metabonomics. In this study, 1471 differentially expressed genes (DEGs) were found between DP and BP. In comparison with SP, a total of 6309 DEGs were detected in BP. Additionally, 6624 DEGs were identified between DP and SP. Moreover, 96 and 117 differentially accumulated metabolites (DAMs) were detected between DP and BP and between BP and SP, respectively. Furthermore, 130 DAMs were identified in total between DP and SP. In each group, a correlation analysis of DAMs and DEGs was performed to examine the regulatory network. The results indicated that the sprouting of tubers is mainly regulated by plant hormone signals, and during the sprouting of tubers, significant changes in metabolic products occur in the body. According to the combined analysis of transcriptomics and metabolomics, multiple metabolites were both positive and negative regulated by genes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zheng, Li, Zhang, Chen, Ge, Li, Tian and Tian.)

Cr(VI) released into the environment inevitably co-exists with other contaminants, such as heavy metal ions, thus altering the performance of bacteria for Cr(VI) reduction; however, the mechanism underlying Cr(VI)-reducing bacterial response to heavy metal ions remains elusive. Herein, we investigate the toxic effects of Cu(II) and Cr(VI) on Cr(VI)-reducing bacterium Pannonibacter phragmitetus D-6 (hereafter D-6), which changes the primary metabolic pattern of Cr(VI). At Cu(II) concentrations of 10-100 mg/L, the efficiency of Cr(VI) reduction increases significantly. The co-exposure of Cr(VI) and Cu(II) induces D-6 to preferentially respond to Cu(II) through electrostatic forces, which is then reduced to Cu(I) outside and inside the bacterial cells. The original pathways for Cr(VI) reduction are weakened via downregulating genes related to Cr(VI) transport and reduction. A new mechanism involving Cu(II)-mediated electron transfer from D-6 to Cr(VI) is elucidated. Specially, Cu(II) accumulates around the cells as an electron shuttle and promotes Cr(VI) reduction. Genes encoding cytochromes involved in electron transfer are significantly up-regulated, thus promoting Cu(II) reduction. The Cu(II)/Cu(I) redox cycle ensures the continuous bioremoval of Cr(VI) in a cycle test. This study reveals an overlooked mechanism for Cr(VI) reduction, which provides theoretical guidance for designing practical microbial process to remediate Cr(VI) contamination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A colorimetric and photothermal dual readout biosensor for Flap endonuclease 1 (FEN1) quantification was developed on the basis of target-prevented gold nanoparticles (AuNPs) aggregation. The exposed 5'-flap of double-flap DNA substrate modified on SAMBs was firstly cleaved by FEN1. Large amount of cleaved 5'-flap remained in the supernatant after simple magnetic separation, which can adsorb on the surface of AuNPs and effectively prevent the dispersed AuNPs from aggregation under high ionic concentration, accompanied with the color changing of the system, which can be recognized by nake eyes easily. The absorption intensity at 528 nm shows a good linear relationship with the increasing FEN1 concentration from 5.0 × 10 -3 to 3.1 × 10 -2 U μL -1 with a LOD of 1.6 × 10 -3 U μL -1  (S/N = 3). Given the aggregated AuNPs have higher photothermal effect than that of the dispersed AuNPs, the target-prevented AuNPs aggregation avoids a sharp increase of temperature for the system under the laser radiation. The temperature change is linearly correlated with the FEN1 concentration in the range of 3.1 × 10 -3 -6.1 × 10 -2 U μL -1 with a LOD of 1.1 × 10 -3 U μL -1 . The whole detection process can be completed within 1 h. The proposed system had been applied to detect FEN1 concentration in serum samples with satisfied results, which can be applied in resource-limited area easily and quickly., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Many evidences have confirmed that chromatin regulator factors (CRs) are involved in the progression of cancer, but its potential mechanism of affecting hepatitis B related hepatocellular carcinoma still needs to be studied. Our study detected the CRs that affect hepatitis B related hepatocellular carcinoma (HBV-HCC) through machine learning analysis, conducted the analysis of immune cells, constructed the relevant risk model and immune function infiltration, and predicted the potential therapeutic drugs. We found that these CRs were significantly related to the immune cells of Macrophages, B cells, CD8 + T cells, etc., and PBK, AURKA, TOP2A and AURKB were the potential risk CRs of HBV-HCC. The expression levels of these four CRs increased in HepG2.2.15 cells and the liver of HBV-HCC patients, consistent with the predicted risk model. Subsequently, ten potential drugs closely related to the risk CRs were finally obtained, experimental research on resveratrol has shown that it can inhibit the proliferation of HepG2.2.15 cells and potentially inhibit the occurrence and development of HBV-HCC. Our study provides novel insights into the function of CRs in HBV-HCC and certain ideas for more accurate targeted therapy.Communicated by Ramaswamy H. Sarma.

There is a huge demand for brewing water in tea consumption, and the sensory flavor of tea infusion is significantly affected by the water used for brewing. To investigate the impact of brewing water on the aroma of tea infusions made from Camelia senensis, the three tea infusions of green, oolong and black tea brewed by six different drinking waters were analyzed by sensory evaluation, solid-phase microextraction, gas chromatography-mass spectrometry, and chemometrics. Brewing water with high pH values (>8.10) and high TDS content (>140 ppm) resulted in a lower overall aroma acceptability for tea infusion, where HCO 3 - , Ca 2+ and Mg 2+ were key influencing ions. A total of 86, 106, and 131 volatiles were identified in green, oolong and black tea infusions, respectively, which were strongly influenced by six different brands of waters. Decanal, dimethyl sulfide, β-ionone and linalool were potent volatiles in tea aroma changes caused by brewing water., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Due to adhesion and rejection of recent traditional materials, it is still challenging to promote the regenerative repair of abdominal wall defects caused by different hernias or severe trauma. However, biomaterials with a high biocompatibility and low immunogenicity have exhibited great potential in the regeneration of abdominal muscle tissue. Previously, we have designed a biological collagen scaffold material combined with growth factor, which enables a fusion protein-collagen binding domain (CBD)-basic fibroblast growth factor (bFGF) to bind and release specifically. Though experiments in rodent animals have indicated the regeneration function of CBD-bFGF modified biological collagen scaffolds, its translational properties in large animals or humans are still in need of solid evidence. In this study, the abdominal wall defect model of Bama miniature pigs was established by artificial operations, and the defective abdominal wall was sealed with or without a polypropylene patch, and unmodified and CBD-bFGF modified biological collagen scaffolds. Results showed that a recurrent abdominal hernia was observed in the defect control group (without the use of mesh). Although the polypropylene patch can repair the abdominal wall defect, it also induced serious adhesion and inflammation. Meanwhile, both kinds of collagen biomaterials exhibited positive effects in repairing abdominal wall defects and reducing regional adhesion and inflammation. However, CBD-bFGF-modified collagen biomaterials failed to induce the regenerative repair reported in rat experiments. In addition, unmodified collagen biomaterials induced abdominal wall muscle regeneration rather than fibrotic repair. These results indicated that the unmodified collagen biomaterials are a better option among translational patches for the treatment of abdominal wall defects.

IQSEC2 (aka BRAG1) is a guanine nucleotide exchange factor (GEF) highly enriched in synapses. As a top neurodevelopmental disorder risk gene, numerous mutations are identified in Iqsec2 in patients with intellectual disabilities accompanied by other developmental, neurological, and psychiatric symptoms, though with poorly understood underlying molecular mechanisms. The atomic structures of IQSECs, together with biochemical analysis, presented in this study reveal an autoinhibition and Ca2+-dependent allosteric activation mechanism for all IQSECs and rationalize how each identified Iqsec2 mutation can alter the structure and function of the enzyme. Transgenic mice modeling two pathogenic variants of Iqsec2 (R359C and Q801P), with one activating and the other inhibiting the GEF activity of the enzyme, recapitulate distinct clinical phenotypes in patients. Our study demonstrates that different mutations on one gene such as Iqsec2 can have distinct neurological phenotypes and accordingly will require different therapeutic strategies., (© 2023 Bai et al.)

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related deaths in China. Rapid and precise evaluation of tumor tissue during lung cancer surgery can reduce operative time and improve negative-margin assessment, thus increasing disease-free and overall survival rates. This study aimed to explore the potential of label-free multiphoton microscopy (MPM) for imaging adenocarcinoma tissues, detecting histopathological features, and distinguishing between normal and cancerous lung tissues. We showed that second harmonic generation (SHG) signals exhibit significant specificity for collagen fibers, enabling the quantification of collagen features in lung adenocarcinomas. In addition, we developed a collagen score that could be used to distinguish between normal and tumor areas at the tumor boundary, showing good classification performance. Our findings demonstrate that MPM imaging technology combined with an image-based collagen feature extraction method can rapidly and accurately detect early-stage lung adenocarcinoma tissues., (© 2023 Wiley-VCH GmbH.)