Lignin with controlled structural properties by N-heterocycle-based deep eutectic solvent extraction.

The complex and heterogeneous nature of the lignin macromolecule has presented a lasting barrier to its utilization. To achieve high lignin yield, the technical lignin extraction process usually severely modifies and condenses the native structure of lignin, which is a critical drawback for its utilization in conversion processes. In addition, there is no method capable of separating lignin from plant biomass with controlled structural properties. Here, we developed an N-heterocycle-based deep eutectic solvent formed between lactic acid and pyrazole (La-Py DES) with a binary hydrogen bonding functionality resulting in a high affinity toward lignin. Up to 93.7% of lignin was extracted from wheat straw biomass at varying conditions from 90 °C to 145 °C. Through careful selection of treatment conditions as well as lactic acid to pyrazole ratios, lignin with controlled levels of ether linkage content, hydroxyl group content, and average molecular weight can be generated. Under mild extraction conditions (90 °C to 120 °C), light-colored native-like lignin can be produced with up to 80% yield, whereas ether linkage-free lignin with low polydispersity can be obtained at 145 °C. Overall, this study offers a new strategy for native lignin extraction and generating lignin with controlled structural properties.

CUNet3+: A Multiscale Connected UNet for the Segmentation of Lung Cancer Cells in Pathology Sections Stained Using Rapid On-Site Cytopathological Evaluation.

Lung cancer is an increasingly serious health problem worldwide, and early detection and diagnosis are crucial for successful treatment. With the development of artificial intelligence and the growth of data volume, machine learning techniques can play a significant role in improving the accuracy of early detection in lung cancer. This study proposes a deep learning-based segmentation algorithm for rapid on-site cytopathological evaluation (ROSE) to enhance the diagnostic efficiency of endobronchial ultrasound-guided transbronchial needle aspiration biopsy (EBUS-TBNA) during surgery. By utilizing the CUNet3+ network model, cell clusters, including cancer cell clusters, can be accurately segmented in ROSE-stained pathological sections. The model demonstrated high accuracy, with an F1-score of 0.9604, recall of 0.9609, precision of 0.9654, and accuracy of 0.9834 on the internal testing data set. It also achieved an area under the receiver-operating characteristic curve of 0.9972 for cancer identification. The proposed algorithm provides time savings for on-site diagnosis, improves EBUS-TBNA efficiency, and outperforms classical segmentation algorithms in accurately identifying lung cancer cell clusters in ROSE-stained images. It effectively reduces over-segmentation, decreases network parameters, and enhances computational efficiency, making it suitable for real-time patient evaluation during surgical procedures.

Individual differences of white matter characteristic along the anterior insula-based fiber tract circuit for pain empathy in healthy women and women with primary dysmenorrhea.

Pain empathy, defined as the ability of one person to understand another person's pain, shows large individual variations. The anterior insula is the core region of the pain empathy network. However, the relationship between white matter (WM) properties of the fiber tracts connecting the anterior insula with other cortical regions and an individual's ability to modulate pain empathy remains largely unclear. In this study, we outline an automatic seed-based fiber streamline (sFS) analysis method and multivariate pattern analysis (MVPA) to predict the levels of pain empathy in healthy women and women with primary dysmenorrhoea (PDM). Using the sFS method, the anterior insula-based fiber tract network was divided into five fiber cluster groups. In healthy women, interindividual differences in pain empathy were predicted only by the WM properties of the five fiber cluster groups, suggesting that interindividual differences in pain empathy may rely on the connectivity of the anterior insula-based fiber tract network. In women with PDM, pain empathy could be predicted by a single cluster group. The mean WM properties along the anterior insular-rostroventral area of the inferior parietal lobule further mediated the effect of pain on empathy in patients with PDM. Our results suggest that chronic periodic pain may lead to maladaptive plastic changes, which could further impair empathy by making women with PDM feel more pain when they see other people experiencing pain. Our study also addresses an important gap in the analysis of the microstructural characteristics of seed-based fiber tract network.

Enhanced stability of M1 protein mediated by a phospho-resistant mutation promotes the replication of prevailing avian influenza virus in mammals.

Avian influenza virus (AIV) can evolve multiple strategies to combat host antiviral defenses and establish efficient infectivity in mammals, including humans. H9N2 AIV and its reassortants (such as H5N6 and H7N9 viruses) pose an increasing threat to human health; however, the mechanisms involved in their increased virulence remain poorly understood. We previously reported that the M1 mutation T37A has become predominant among chicken H9N2 isolates in China. Here, we report that, since 2010, this mutation has also been found in the majority of human isolates of H9N2 AIV and its emerging reassortants. The T37A mutation of M1 protein enhances the replication of H9N2 AIVs in mice and in human cells. Interestingly, having A37 instead of T37 increases the M1 protein stability and resistance to proteasomal degradation. Moreover, T37 of the H9N2 M1 protein is phosphorylated by protein kinase G (PKG), and this phosphorylation induces the rapid degradation of M1 and reduces viral replication. Similar effects are also observed in the novel H5N6 virus. Additionally, ubiquitination at K187 contributes to M1-37T degradation and decreased replication of the virus harboring T37 in the M1 protein. The prevailing AIVs thereby evolve a phospho-resistant mutation in the M1 protein to avoid viral protein degradation by host factors, which is advantageous in terms of replication in mammalian hosts.

p21 restricts influenza A virus by perturbing the viral polymerase complex and upregulating type I interferon signaling.

Many cellular genes and networks induced in human lung epithelial cells infected with the influenza virus remain uncharacterized. Here, we find that p21 levels are elevated in response to influenza A virus (IAV) infection, which is independent of p53. Silencing, pharmacological inhibition or deletion of p21 promotes virus replication in vitro and in vivo, indicating that p21 is an influenza restriction factor. Mechanistically, p21 binds to the C-terminus of IAV polymerase subunit PA and competes with PB1 to limit IAV polymerase activity. Besides, p21 promotes IRF3 activation by blocking K48-linked ubiquitination degradation of HO-1 to enhance type I interferons expression. Furthermore, a synthetic p21 peptide (amino acids 36 to 43) significantly inhibits IAV replication in vitro and in vivo. Collectively, our findings reveal that p21 restricts IAV by perturbing the viral polymerase complex and activating the host innate immune response, which may aid the design of desperately needed new antiviral therapeutics.

Angularly offset multiline dispersive optical phased array enabling large field of view and plateau envelope.

We propose and demonstrate an angularly offset multiline (AOML) dispersive silicon nitride optical phased array (OPA) that enables efficient line beam scanning with an expanded field of view (FOV) and plateau envelope. The suggested AOML OPA incorporates multiline OPA units, which were seamlessly integrated with a 45° angular offset through a thermo-optic switch based on a multimode interference coupler, resulting in a wide FOV that combines three consecutive scanning ranges. Simultaneously, a periodic diffraction envelope rendered by the multiline OPA units contributes to reduced peak intensity fluctuation of the main lobe across the large FOV. An expedient polishing enabling the angled facet was diligently accomplished through the implementation of oblique polishing techniques applied to the 90° angle of the chip. For each dispersive OPA unit, we engineered an array of delay lines with progressively adjustable delay lengths, enabling a passive wavelength-tunable beam scanning. Experimental validation of the proposed OPA revealed efficient beam scanning, achieved by wavelength tuning from 1530 to 1600 nm and seamless switching between multiline OPAs, yielding an FOV of 152° with a main lobe intensity fluctuation of 2.8 dB. The measured efficiency of dispersive scanning was estimated at 0.97°/nm, as intended.

Optical characterization of a fiber Fabry-Perot cavity: precision measurement of intra-cavity loss, transmittance, and reflectance.

We propose and demonstrate a method for characterizing the individual mirror parameters of a fiber Fabry-Perot cavity (FFPC). By measuring the reflection and transmission spectra of the FFPC with an incident laser propagating from the two mirrors of the FFPC and considering several normal or unique losses, the transmittance, reflectance, and intra-cavity loss of the individual mirrors can be determined. Due to the intrinsic limitation of cavity length, traditional powerful methods, such as the cavity ring-down technique, are not applicable to FFPCs for characterizing the parameters of individual mirrors. This scheme provides a dependable method for assessing FFPC mirrors and provides a significant capability for the implementation of strong-coupling cavity quantum electrodynamics based on FFPCs.

Protease SfpB plays an important role in cell membrane stability and immune system evasion in Streptococcus agalactiae.

Bacteria possess the ability to develop diverse and ingenious strategies to outwit the host immune system, and proteases are one of the many weapons employed by bacteria. This study sought to identify S. agalactiae additional serine protease and determine its role in virulence. The S. agalactiae THN0901 genome features one S8 family serine peptidase B (SfpB), acting as a secreted and externally exposed entity. A S8 family serine peptidase mutant strain (ΔsfpB) and complement strain (CΔsfpB) were generated through homologous recombination. Compared to the wild-type strain THN0901, the absorption of EtBr dyes was significantly reduced (P < 0.01) in ΔsfpB, implying an altered cell membrane permeability. In addition, the ΔsfpB strain had a significantly lower survival rate in macrophages (P < 0.01) and a 61.85 % lower adhesion ability to the EPC cells (P < 0.01) compared to THN0901. In the in vivo colonization experiment using tilapia as a model, 210 fish were selected and injected with different bacterial strains at a concentration of 3 × 106 CFU/tail. At 6, 12, 24, 48, 72 and 96 h post-injection, three fish were randomly selected from each group and their brain, liver, spleen, and kidney tissues were isolated. Subsequently, it was demonstrated that the ΔsfpB strain exhibited a markedly diminished capacity for colonization in tilapia. Additionally, the cumulative mortality of ΔsfpB in fish after intraperitoneal injection was reduced by 19.92-23.85 %. In conclusion, the findings in this study have demonstrated that the SfpB plays a significant role in S. agalactiae cell membrane stability and immune evasion. The immune evasion is fundamental for the development and transmission of invasive diseases, the serine protease SfpB may be a promising candidate for the development of antimicrobial agents to reduce the transmission of S. agalactiae.

Measurement of Nanofiber Mechanical Flexural Modes Based on Near-Field Scattering.

We systematically investigated the intrinsic mechanical flexural modes of tapered optical fibers (TOFs) with a high aspect ratio up to 3×10^{4}. Based on the near-field scattering of the hemispherical microfiber tip to the vibrating TOF evanescent field, we detected more than 320 ordered intrinsic mechanical modes through the TOF transmission spectra which was enhanced by 72 dB compared to without near-field scattering. The trend of the vibration amplitude with the mode order was similar to pendulum waves. Our results open a pathway to study the mechanical modes of photonic microstructures-nanostructures that are expected to be used in waveguide QED, cavity optomechanical, and optical sensing.

A real-world study of the effectiveness and safety of apatinib-based regimens in metastatic triple-negative breast cancer.

PURPOSE: This investigation sought to examine the efficacy and safety of low-dose apatinib used alongside chemotherapy in the clinical management of patients with metastatic triple-negative breast cancer (TNBC) within a real-world setting, whilst comparing the outcomes with those treated solely with chemotherapy. METHODS: This case series study analyzed clinical data and treatment outcomes of 163 patients with metastatic TNBC who underwent rescue treatment at the Medical Oncology Department of Clinical Oncology, Fujian Cancer Hospital, School of Fujian Medical University, China, between October 2011 and January 2023. All the patients underwent rescue treatment with either chemotherapy alone or apatinib (250 mg/day) combined with chemotherapy. The study's primary outcome was progression-free survival (PFS), whereas the secondary outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles. RESULTS: The study was designed to compare two groups [1]. Out of the 163 TNBC patients who participated in the study, 107 individuals (65.6%) received treatment based on chemotherapy, whereas 56 patients (34.4%) were given treatment based on a combination of low-dose apatinib (250 mg/day) and other treatments, including chemotherapy. After propensity score matching (PSM), the objective response rate (ORR) and disease control rate (DCR) of patients with advanced triple-negative breast cancer (TNBC) who received apatinib-based treatment were 50.0 and 90.0%, respectively, while they were 6.7 and 20.0%, respectively, for the chemotherapy-based group (P < 0.001). The group that received apatinib-based treatment showed superior results in both PFS and OS compared to the group that received chemotherapy. The median PFS and OS for the apatinib-based group were 7.8 and 20.3 months, respectively, while they were only 2.2 months and 9.0 months, respectively, for the chemotherapy-based group (P < 0.001) [2]. Patients who were administered combo therapies, including PD-1 inhibitors, were excluded. In total, 97 patients received chemotherapy alone, while 34 patients were treated with apatinib in combination with chemotherapy. After propensity score matching (PSM), the ORR and DCR for the total group who received combo therapies were 44.4 and 81.5%, respectively, while they were 11.1 and 22.2%, respectively, for the chemotherapy alone group (P < 0.001). The group receiving both apatinib and chemotherapy displayed notable advantages over the group solely receiving chemotherapy in regards to PFS and OS for the entirety of the population. The PFS was found to be 7.8 months in comparison to 2.1 months (P < 0.001) and the OS was 21.1 months in contrast to 9.0 months (P < 0.001). Apatinib combined with chemotherapy induced grade 3/4 hematological toxicities, including neutropenia (8.8%) and thrombocytopenia (2.9%). Additionally, non-hematological toxicities were commonly observed, such as Hand-foot syndrome (35.3%), proteinuria (26.5%), hypertension (61.8%), higher alanine aminotransferase levels (26.5%), and fatigue (35.3%). The most frequent non-hematological grade 3/4 toxicities were Hand-foot syndrome (2.9%) and hypertension (5.9%). The study did not report any fatal adverse effects. CONCLUSIONS: The combination of low-dose apatinib with chemotherapy has proven to be more effective than chemotherapy alone in treating metastatic triple-negative breast cancer (TNBC). Additionally, the occurrence of grade 3/4 non-hematologic toxicities was significantly lower compared to the recommended dose of apatinib.

Re-exploration of tetrahydro-ß-carboline scaffold: Discovery of selective histone deacetylase 6 inhibitors with neurite outgrowth-promoting and neuroprotective activities.

Histone deacetylase 6 (HDAC6) has drawn more and more attention for its potential application in Alzheimer's disease (AD) therapy. A series of tetrahydro-ß-carboline (THßC) hydroxamic acids with aryl linker were synthesized. In enzymatic assay, all compounds exhibited nanomolar IC50 values. The most promising compound 11d preferentially inhibited HDAC6 (IC50, 8.64 nM) with approximately 149-fold selectivity over HDAC1. Molecular simulation revealed that the hydroxamic acid of 11d could bind to the zinc ion by a bidentate chelating manner. In vitro, 11d induced neurite outgrowth of PC12 cells without producing toxic effects and showed obvious neuroprotective activity in a model of H2O2-induced oxidative stress.

Nirmatrelvir and ritonavir for inpatients with severe or critical COVID-19 beyond five days of symptom onset: a propensity score-matched, multicenter, retrospective cohort study.

BACKGROUND: There is an urgent need for therapeutic strategies for inpatients with severe or critical COVID-19. The evaluation of the clinical benefits of nirmatrelvir and ritonavir (Nmr/r) for these patients beyond five days of symptom onset is insufficient. METHODS: A new propensity score-matched cohort was constructed by using multicenter data from 6695 adult inpatients with COVID-19 from December 2022 to February 2023 in China after the epidemic control measures were lifted across the country. The severity of disease of the inpatients was based on the tenth trial edition of the Guidelines on the Diagnosis and Treatment of COVID-19 in China. The symptom onset of 1870 enrolled severe or critical inpatients was beyond five days, and they received either Nmr/r plus standard treatment or only standard care. The ratio of patients whose SOFA score improved more than 2 points, crucial respiratory endpoints, changes in inflammatory markers, safety on the seventh day following the initiation of Nmr/r treatment, and length of hospital stay were evaluated. RESULTS: In the Nmr/r group, on Day 7, the number of patients with an improvement in SOFA score ≥ 2 was much greater than that in the standard treatment group (P = 0.024) without a significant decrease in glomerular filtration rate (P = 0.815). Additionally, the rate of new intubation was lower (P = 0.004) and the no intubation days were higher (P = 0.003) in the first 7 days in the Nmr/r group. Other clinical benefits were limited. CONCLUSIONS: Our study may provide new insight that inpatients with severe or critical COVID-19 beyond five days of symptom onset benefit from Nmr/r. Future studies, particularly randomized controlled trials, are necessary to verify the above findings.

Bayesian metamodeling of complex biological systems across varying representations.

Comprehensive modeling of a whole cell requires an integration of vast amounts of information on various aspects of the cell and its parts. To divide and conquer this task, we introduce Bayesian metamodeling, a general approach to modeling complex systems by integrating a collection of heterogeneous input models. Each input model can in principle be based on any type of data and can describe a different aspect of the modeled system using any mathematical representation, scale, and level of granularity. These input models are 1) converted to a standardized statistical representation relying on probabilistic graphical models, 2) coupled by modeling their mutual relations with the physical world, and 3) finally harmonized with respect to each other. To illustrate Bayesian metamodeling, we provide a proof-of-principle metamodel of glucose-stimulated insulin secretion by human pancreatic ß-cells. The input models include a coarse-grained spatiotemporal simulation of insulin vesicle trafficking, docking, and exocytosis; a molecular network model of glucose-stimulated insulin secretion signaling; a network model of insulin metabolism; a structural model of glucagon-like peptide-1 receptor activation; a linear model of a pancreatic cell population; and ordinary differential equations for systemic postprandial insulin response. Metamodeling benefits from decentralized computing, while often producing a more accurate, precise, and complete model that contextualizes input models as well as resolves conflicting information. We anticipate Bayesian metamodeling will facilitate collaborative science by providing a framework for sharing expertise, resources, data, and models, as exemplified by the Pancreatic ß-Cell Consortium.

PtMo-Au Metalloenzymes Regulated Tumor Microenvironment for Enhanced Sonodynamic/Chemodynamic/Starvation Synergistic Therapy.

The clinical application of sonodynamic therapy (SDT) is greatly limited by the low quantum yield of sonosensitizers and tumor microenvironment (TME). Herein, PtMo-Au metalloenzyme sonosensitizer is synthesized by modulating energy band structure of PtMo with Au nanoparticles. The surface deposition of Au simultaneously solves the carrier recombination and facilitates the separation of electrons (e- ) and holes (h+ ), effectively improving the reactive oxygen species (ROS) quantum yield under ultrasound (US). The catalase-like activity of PtMo-Au metalloenzymes alleviates hypoxia TME, thus enhancing the SDT-induced ROS generation. More importantly, tumor overexpressed glutathione (GSH) can serve as the hole scavenger, which is accompanied by a persistent depletion of the GSH, thus inactivating GPX4 for the accumulation of lipid peroxides. The distinctly facilitated SDT-induced ROS production is coupled with chemodynamic therapy (CDT)-induced hydroxyl radicals (•OH) to exacerbate ferroptosis. Furthermore, Au with glucose oxidase mimic activity can not only inhibit intracellular adenosine triphosphate (ATP) production and induce tumor cell starvation but also generate H2 O2 to facilitate CDT. In general, this PtMo-Au metalloenzyme sonosensitizer optimizes the defects of conventional sonosensitizers through surface deposition of Au to regulate TME, providing a novel perspective for US-based tumor multimodal therapy.

Prediction of gene co-expression from chromatin contacts with graph attention network.

MOTIVATION: The technology of high-throughput chromatin conformation capture (Hi-C) allows genome-wide measurement of chromatin interactions. Several studies have shown statistically significant relationships between gene-gene spatial contacts and their co-expression. It is desirable to uncover epigenetic mechanisms of transcriptional regulation behind such relationships using computational modeling. Existing methods for predicting gene co-expression from Hi-C data use manual feature engineering or unsupervised learning, which either limits the prediction accuracy or lacks interpretability. RESULTS: To address these issues, we propose HiCoEx (Hi-C predicts gene co-expression), a novel end-to-end framework for explainable prediction of gene co-expression from Hi-C data based on graph neural network. We apply graph attention mechanism to a gene contact network inferred from Hi-C data to distinguish the importance among different neighboring genes of each gene, and learn the gene representation to predict co-expression in a supervised and task-specific manner. Then, from the trained model, we extract the learned gene embeddings as a model interpretation to distill biological insights. Experimental results show that HiCoEx can learn gene representation from 3D genomics signals automatically to improve prediction accuracy, and make the black box model explainable by capturing some biologically meaningful patterns, e.g., in a gene contact network, the common neighbors of two central genes might contribute to the co-expression of the two central genes through sharing enhancers. AVAILABILITY AND IMPLEMENTATION: The source code is freely available at https://github.com/JieZheng-ShanghaiTech/HiCoEx. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

H9N2 virus-derived M1 protein promotes H5N6 virus release in mammalian cells: Mechanism of avian influenza virus inter-species infection in humans.

H5N6 highly pathogenic avian influenza virus (HPAIV) clade 2.3.4.4 not only exhibits unprecedented intercontinental spread in poultry, but can also cause serious infection in humans, posing a public health threat. Phylogenetic analyses show that 40% (8/20) of H5N6 viruses that infected humans carried H9N2 virus-derived internal genes. However, the precise contribution of H9N2 virus-derived internal genes to H5N6 virus infection in humans is unclear. Here, we report on the functional contribution of the H9N2 virus-derived matrix protein 1 (M1) to enhanced H5N6 virus replication capacity in mammalian cells. Unlike H5N1 virus-derived M1 protein, H9N2 virus-derived M1 protein showed high binding affinity for H5N6 hemagglutinin (HA) protein and increased viral progeny particle release in different mammalian cell lines. Human host factor, G protein subunit beta 1 (GNB1), exhibited strong binding to H9N2 virus-derived M1 protein to facilitate M1 transport to budding sites at the cell membrane. GNB1 knockdown inhibited the interaction between H9N2 virus-derived M1 and HA protein, and reduced influenza virus-like particles (VLPs) release. Our findings indicate that H9N2 virus-derived M1 protein promotes avian H5N6 influenza virus release from mammalian, in particular human cells, which could be a major viral factor for H5N6 virus cross-species infection.

Sleep Patterns Modify the Association between Vitamin D Status and Coronary Heart Disease: Results from NHANES 2005-2008.

BACKGROUND: Although an increased risk of coronary heart disease (CHD) has been reported in individuals with low vitamin D status, this remains controversial. Growing evidence suggests that sleep behaviors may influence vitamin D endocrine functions. OBJECTIVES: We explored the association between serum 25-hydroxyvitamin D [[25(OH)D] concentrations and CHD and whether sleep behaviors modify this relationship. METHODS: A cross-sectional analysis of 7511 adults aged ≥20 y in 2005-2008 National Health and Nutrition Examination Survey (NHANES) that included serum 25(OH)D concentrations and provided information on sleep behaviors and history of CHD was performed. Logistic regression models were used to assess the association between serum 25(OH)D concentrations and CHD, whereas stratified analyses and multiplicative interaction tests were used to evaluate the modification effect of overall sleep patterns and each sleep factor on this relationship. The overall sleep patterns integrated 4 sleep behaviors (sleep duration, snoring, insomnia, and daytime sleepiness) in the form of healthy sleep score. RESULTS: Serum 25(OH)D concentrations were inversely associated with risk of CHD (P < 0.01). Hypovitaminosis D [serum 25(OH)D <50nmol/L] was associated with a 71% increased risk of CHD (OR: 1.71; 95% CI: 1.28, 2.28; P < 0.01) compared with that in participants with sufficient vitamin D [serum 25(OH)D ≥75nmol/L], and the association was more evident and stable among participants with poor sleep patterns (P-interaction < 0.01). Among the individual sleep behaviors, sleep duration had the strongest interaction with 25(OH)D (P-interaction < 0.05). The association between serum 25(OH)D concentrations and risk of CHD was more pronounced in participants with sleep duration <7 h/d or >8 h/d compared with those with sleep duration 7-8 h/d. CONCLUSIONS: These findings suggest that the influence of lifestyle-related behavioral risk factors, such as sleep behaviors (especially sleep duration), need to be considered when evaluating the association between serum 25(OH)D concentrations and CHD as well as the clinical benefits of vitamin D supplementation.

Application of starch-based nanoparticles and cyclodextrin for prebiotics delivery and controlled glucose release in the human gut: a review.

Starches are a major constituent of staple foods and are the main source of energy in the human diet (55-70%). In the gastrointestinal tract, starches are hydrolyzed into glucose by α-amylase and α-glucosidase, which leads to a postprandial glucose elevation. High levels of blood glucose levels over sustained periods may promote type 2 diabetes mellitus (T2DM) and obesity. Increasing consumption of starchy foods with a lower glycemic index may therefore contribute to improved health. In this paper, the preparation and properties of several starch-based nanoparticles (SNPs) and cyclodextrins (CDs) derivatives are reviewed. In particular, we focus on the various mechanisms responsible for the ability of these edible nanomaterials to modulate glucose release and the gut microbiome in the gastrointestinal tract. The probiotic functions are achieved through encapsulation and protection of prebiotics or bioactive components in foods or the human gut. This review therefore provides valuable information that could be used to design functional foods for improving human health and wellbeing.

Molecular phylogeography and historical demography of a widespread herbaceous species from eastern North America, Podophyllum peltatum.

PREMISE: Glacial/interglacial cycles and topographic complexity are both considered to have shaped today's diverse phylogeographic patterns of taxa from unglaciated eastern North America (ENA). However, few studies have focused on the phylogeography and population dynamics of wide-ranging ENA herbaceous species occurring in forest understory habitat. We examined the phylogeographic pattern and evolutionary history of Podophyllum peltatum L., a widely distributed herb inhabiting deciduous forests of ENA. METHODS: Using chloroplast DNA (cpDNA) sequences and nuclear microsatellite loci, we investigated the population structure and genetic diversity of the species. Molecular dating, demographic history analyses, and ecological niche modeling were also performed to illustrate the phylogeographic patterns. RESULTS: Our cpDNA results identified three main groups that are largely congruent with boundaries along the Appalachian Mountains and the Mississippi River, two major geographic barriers in ENA. Populations located to the east of the Appalachians and along the central Appalachians exhibited relatively higher levels of genetic diversity. Extant lineages may have diverged during the late Miocene, and range expansions of different groups may have happened during the Pleistocene glacial/interglacial cycles. CONCLUSIONS: Our findings indicate that geographic barriers may have started to facilitate the population divergence in P. peltatum before the Pleistocene. Persistence in multiple refugia, including areas around the central Appalachians during the Quaternary glacial period, and subsequent expansions under hospitable climatic condition, especially westward expansion, are likely responsible for the species' contemporary genetic structure and phylogeographic pattern.

Efficacy and Safety of Finerenone for Prevention of Cardiovascular Events in Type 2 Diabetes Mellitus With Chronic Kidney Disease: A Meta-analysis of Randomized Controlled Trials.

ABSTRACT: Only a few meta-analyses evaluated the effect of finerenone on cardiovascular events in type 2 diabetes mellitus with chronic kidney disease. The main aim of this meta-analysis was to gain more reliable assessments of the efficacy and safety of finerenone for prevention of cardiovascular events in diabetic kidney disease. We searched for finerenone in the treatment of diabetic kidney disease from database (PubMed, Embase, and ClinicalTrials.gov ) until December 30, 2021. Relative risks (RRs) with 95% confidence intervals (CIs) calculated by the Mantel-Haenszel random-effects model were used as summary statistics for the categorical data. We included 4 studies that met the inclusion criteria with 13,943 participants. The finerenone group demonstrated a great benefit in reducing the incidence of major adverse cardiac events (RR: 0.88; 95% CI 0.80-0.96; P = 0.003), all-cause mortality (RR: 0.89; 95% CI 0.80-0.99; P = 0.04), myocardial infarction (RR: 0.79; 95% CI 0.67-0.92; P = 0.003), and new-onset hypertension (RR: 0.71; 95% CI 0.62-0.81; P < 0.00001). No difference was found in adverse events between the finerenone and placebo groups (RR: 1.00; 95% CI [0.98-1.01], P = 0.59), whereas a higher risk of hyperkalemia was observed in the finerenone group than in the placebo group (RR = 2.04, 95% CI 1.80-2.32; P < 0.00001). Besides, cerebrovascular events and new-onset atrial fibrillation did not increase in patients taking finerenone. Overall, finerenone treatment showed a great benefit of reducing the risk of major adverse cardiac events, all-cause mortality, myocardial infarction, and new-onset hypertension events in patients with type 2 diabetes mellitus and chronic kidney disease.