Nonlinear geometric phase coded ferroelectric nematic fluids for nonlinear soft-matter photonics.

Simultaneous manipulation of multiple degrees of freedom of light lies at the heart of photonics. Nonlinear wavefront shaping offers an exceptional way to achieve this goal by converting incident light into beams of new frequencies with spatially varied phase, amplitude, and angular momenta. Nevertheless, the reconfigurable control over structured light fields for advanced multimode nonlinear photonics remains a grand challenge. Here, we propose the concept of nonlinear geometric phase in an emerging ferroelectric nematic fluid, of which the second-order nonlinear susceptibility carries spin-dependent nonlinearity phase. A case study with photopatterned q-plates demonstrates the generation of second-harmonic optical vortices with spin-locked topological charges by using cascaded linear and nonlinear optical spin-orbit interactions. Furthermore, we present the dynamic tunability of second-harmonic structured light through temperature, electric field, and twisted elastic force. The proposed strategy opens new avenues for reconfigurable nonlinear photonics, with potential applications in optical communications, quantum computing, high-resolution imaging, etc.

Metabolic network rewiring and temperature-dependent regulation for enhanced 3-dehydroshikimate production in Escherichia coli.

The cyclohexane organic acid 3-dehydroshikimate (DHS) has potent antioxidant activity and is widely utilised in chemical and pharmaceutical industries. However, its production requires a long fermentation with a suboptimal yield and low productivity, and a disproportionate growth-to-production ratio impedes the upscaling of DHS synthesis in microbial cell factories. To overcome these limitations, competing and degradation pathways were knocked-out and key enzymes were balanced in an engineered Escherichia coli production strain, resulting in 12.2 g/L DHS. Furthermore, to achieve equilibrium between cell growth and DHS production, a CRISPRi-based temperature-responsive multi-component repressor system was developed to dynamically control the expression of critical genes (pykF and aroE), resulting in a 30-fold increase in DHS titer. After 33 h fermentation in 5 L bioreactor, the DHS titer, productivity and yield reached 94.2 g/L, 2.8 g/L/h and 55 % glucose conversion, respectively. The results provided valuable insight into the production of DHS and its derivatives.

Functional roles of the interaction of Moa1 with CENP-C and Rec8 in meiosis of Schizosaccharomyces pombe.

The localization of the meiotic specific regulatory molecule Moa1 to the centromere is regulated by the kinetochore protein CENP-C, and participates in the cohesion of sister chromatids in the centromere region mediated by the cohesin Rec8. To examine the interaction of these proteins, we analyzed the interactions between Moa1 and Rec8, CENP-C by yeast two-hybrid assays and identified several amino acid residues in Moa1 required for the interaction with CENP-C and Rec8. The results revealed that the interaction between Moa1 and CENP-C is crucial for the Moa1 to participate in the regulation of monopolar attachment of sister kinetochores. However, mutation at S143 and T150 of Moa1, which are required for interaction with Rec8 in the two-hybrid assay, did not show significant defects. Mutations in amino acid residues may not be sufficient to interfere with the interaction between Moa1 and Rec8 in vivo. Further research is needed to determine the interaction domain between Moa1 and Rec8. This study revealed specific amino acid sites at which Moa1 affects the meiotic homologous chromosome segregation, providing a deeper understanding of the mechanism of meiotic chromosome segregation.

Developing an Optimized Protocol for Regeneration and Transformation in Pepper.

Capsicum annuum L. is extensively cultivated in subtropical and temperate regions globally, respectively, when grown in a medium with 8 holding significant economic importance. Despite the availability of genome sequences and editing tools, gene editing in peppers is limited by the lack of a stable regeneration and transformation method. This study assessed regeneration and transformation protocols in seven chili pepper varieties, including CM334, Zunla-1, Zhongjiao6 (ZJ6), 0818, 0819, 297, and 348, in order to enhance genetic improvement efforts. Several explants, media compositions, and hormonal combinations were systematically evaluated to optimize the in vitro regeneration process across different chili pepper varieties. The optimal concentrations for shoot formation, shoot elongation, and rooting in regeneration experiments were determined as 5 mg/L of 6-Benzylaminopurine (BAP) with 5 mg/L of silver nitrate (AgNO3), 0.5 mg/L of Gibberellic acid (GA3), and 1 mg/L of Indole-3-butyric acid (IBA), respectively. The highest regeneration rate of 41% was observed from CM334 cotyledon explants. Transformation optimization established 300 mg/L of cefotaxime for bacterial control, with a 72-h co-cultivation period at OD600 = 0.1. This study optimizes the protocols for chili pepper regeneration and transformation, thereby contributing to genetic improvement efforts.

Fine Mapping and Candidate Gene Analysis of Two Major Quantitative Trait Loci, qFW2.1 and qFW3.1, Controlling Fruit Weight in Pepper (Capsicum annuum).

Fruit weight is an important agronomic trait in pepper production and is closely related to yield. At present, many quantitative trait loci (QTL) related to fruit weight have been found in pepper; however, the genes affecting fruit weight remain unknown. We analyzed the fruit weight-related quantitative traits in an intraspecific Capsicum annuum cross between the cultivated species blocky-type pepper, cv. Qiemen, and the bird pepper accession, "129-1" (Capsicum annuum var. glatriusculum), which was the wild progenitor of C. annuum. Using the QTL-seq combined with the linkage-based QTL mapping approach, QTL detection was performed; and two major effects of QTL related to fruit weight, qFW2.1 and qFW3.1, were identified on chromosomes 2 and 3. The qFW2.1 maximum explained 12.28% of the phenotypic variance observed in two F2 generations, with the maximum LOD value of 11.02, respectively; meanwhile, the qFW3.1 maximum explained 15.50% of the observed phenotypic variance in the two F2 generations, with the maximum LOD value of 11.36, respectively. qFW2.1 was narrowed down to the 1.22 Mb region using homozygous recombinant screening from BC2S2 and BC2S3 populations, while qFW3.1 was narrowed down to the 4.61Mb region. According to the transcriptome results, a total of 47 and 86 differentially expressed genes (DEGs) in the candidate regions of qFW2.1 and qFW3.1 were identified. Further, 19 genes were selected for a qRT-PCR analysis based on sequence difference combined with the gene annotation. Finally, Capana02g002938 and Capana02g003021 are the most likely candidate genes for qFW2.1, and Capana03g000903 may be a candidate gene for qFW3.1. Taken together, our results identified and fine-mapped two major QTL for fruit weight in pepper that will facilitate marker-assistant breeding for the manipulation of yield in pepper.

NOX4-mediated astrocyte ferroptosis in Alzheimer's disease.

This study investigates NADPH oxidase 4 (NOX4) involvement in iron-mediated astrocyte cell death in Alzheimer's Disease (AD) using single-cell sequencing data and transcriptomes. We analyzed AD single-cell RNA sequencing data, identified astrocyte marker genes, and explored biological processes in astrocytes. We integrated AD-related chip data with ferroptosis-related genes, highlighting NOX4. We validated NOX4's role in ferroptosis and AD in vitro and in vivo. Astrocyte marker genes were enriched in AD, emphasizing their role. NOX4 emerged as a crucial player in astrocytic ferroptosis in AD. Silencing NOX4 mitigated ferroptosis, improved cognition, reduced Aß and p-Tau levels, and alleviated mitochondrial abnormalities. NOX4 promotes astrocytic ferroptosis, underscoring its significance in AD progression.

The effect of centromere protein Fta2 phosphorylation during meiosis.

During meiosis, defects in cohesin localization within the centromere region can result in various diseases. Accurate cohesin localization depends on the Mis4-Ssl3 loading complex. Although it is known that cohesin completes the loading process with the help of the loading complex, the mechanisms underlying its localization in the centromere region remain unclear. Previous studies suggest cohesin localization in the centromere is mediated by phosphorylation of centromeric proteins. In this study, we focused on the Fta2 protein, a component of the Sim4 centromere protein complex. Using bioinformatics methods, potential phosphorylation sites were identified, and fta2-9A and fta2-9D mutants were constructed in Schizosaccharomyces pombe. The phenotypes of these mutants were characterized through testing thiabendazole (TBZ) sensitivity and fluorescent microscopy localization. Results indicated that Fta2 phosphorylation did not impact mitosis but affected chromosome segregation during meiosis. This study suggests that Fta2 phosphorylation is vital for meiosis and may be related to the specific localization of cohesin during this process.

Construction of ROS-Responsive Hyaluronic Acid Modified Paclitaxel and Diosgenin Liposomes and Study on Synergistic Enhancement of Anti-Ovarian Cancer Efficacy.

Purpose: Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG2000-HA and DSPE-PEG2000-TK-PEG5000, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration. Methods and Results: PEG-TK-HA-PDLPs were prepared by film dispersion, with ideal physicochemical properties and exhibits active targeting for enhanced cellular uptake. The ZIP synergy score for PTX and Dios was calculated using the online SynergyFinder software to be 3.15, indicating synergy. In vitro results showed that PEG-TK-HA-PDLPs were highly cytotoxic to ID8 cells, induced ID8 cell apoptosis, and inhibited ID8 cell migration and invasion. In vivo studies showed that PEG-TK-HA-PDLPs could prolong the circulation time in the blood, accumulate significantly in the tumor site, and effectively fight against angiogenesis with significant anti-tumor effects. Conclusion: The production of PEG-TK-HA-PDLPs is an effective strategy for the treatment of OC.

Plasma levels of bactericidal/permeability-increasing protein correlate with systemic inflammation in acute coronary syndrome.

Background: Neutrophils play important roles in atherosclerosis and atherothrombosis. Bactericidal/permeability-increasing protein (BPI) is mainly expressed in the granules of human neutrophils in response to inflammatory stress. This observational, cross-sectional study investigated the plasma level of BPI in patients with acute coronary syndrome (ACS) and its correlation with blood neutrophil counts and circulating inflammatory biomarkers. Methods: A total of 367 patients who had acute chest pain and who were admitted to our hospital for coronary angiography (CAG) and/or percutaneous coronary intervention (PCI) from May 1, 2020 to August 31, 2020 were recruited. Among them, 256 had a cardiac troponin value above the 99th percentile upper reference limit and were diagnosed with ACS. The remaining patients (n = 111) were classified as non-ACS. The TIMI and GRACE scores were calculated at admission. The Gensini score based on CAG was used to determine atherosclerotic burden. Plasma levels of interleukin (IL)-1ß, myeloperoxidase-DNA (MPO-DNA), high sensitivity C-reactive protein (hs-CRP), S100A8/A9, and BPI were measured using enzyme-linked immunosorbent assays. Correlations of plasma BPI levels with examination scores and levels of circulating inflammatory biomarkers were explored. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic efficacy of BPI for ACS and myocardial infarction. Results: Patients in the ACS group showed significantly higher plasma BPI levels compared to the non-ACS group (46.42 ± 16.61 vs. 16.23 ± 6.19 ng/mL, p < 0.05). Plasma levels of IL-1ß, MPO-DNA, hs-CRP, and S100A8/A9 in the ACS group were also significantly higher than those in the non-ACS group (all p < 0.05). In addition, plasma BPI levels were positively correlated with the TIMI, GRACE, and Gensini scores (r = 0.176, p = 0.003; r = 0.320, p < 0.001; r = 0.263, p < 0.001, respectively) in patients with ACS. Plasma BPI levels were also positively correlated with blood neutrophil counts (r = 0.266, p < 0.001) and levels of circulating inflammatory biomarkers (IL-1ß, r = 0.512; MPO-DNA, r = 0.452; hs-CRP, r = 0.554; S100A8/A9, r = 0.434; all p < 0.001) in patients with ACS. ROC curve analysis revealed that the diagnostic efficacy of BPI for ACS was not inferior to that of IL-1ß, MPO-DNA, hs-CRP, S100A8/A9, or blood neutrophil counts. ROC analysis also showed that the diagnostic efficacy of BPI for myocardial infarction was not inferior to that of creatine kinase (CK)-MB or cardiac troponin I. Conclusion: BPI is associated with systemic inflammation in ACS and may be involved in the process of atherosclerosis and atherothrombosis. The potential of BPI as a prognostic and diagnostic biomarker for ACS should be investigated in clinical settings.

Ssu72 phosphatase deficiency leads to spindle crossing during the second meiotic division process.

Ssu72 is a component of the yeast cleavage/polyadenylation factor (CPF) complex, which catalyzes the dephosphorylation of the C-terminal domain (CTD) of RNA polymerase II at S5-P and S7-P. It has been shown that Ssu72 phosphatase is involved in regulating chromosome cohesion during mitosis. To further clarify whether Ssu72 phosphatase affects chromosome separation during meiotic division in Schizosaccharomyces pombe, we utilized green fluorescent protein (GFP) to label centromeres and red fluorescent protein to label microtubule protein Atb2. The entire meiotic chromosome separation process of ssu72∆ cells was observed in real-time under fluorescence microscope. It was found that two spindles of ssu72∆ cells crossed during the metaphase and anaphase of the second meiotic division, and this spindle crossing led to a new type of spore defect distribution pattern. The results of this study can provide important reference significance for studying the roles of phosphatase Ssu72 in higher organisms.

Minocycline in the eradication of Helicobacter pylori infection: A systematic review and meta-analysis.

BACKGROUND: Difficulty in obtaining tetracycline, increased adverse reactions, and relatively complicated medication methods have limited the clinical application of the classic bismuth quadruple therapy. Therefore, the search for new alternative drugs has become one of the research hotspots. In recent years, minocycline, as a semisynthetic tetracycline, has demonstrated good potential for eradicating Helicobacter pylori (H. pylori) infection, but the systematic evaluation of its role remains lacking. AIM: To explore the efficacy, safety, and compliance of minocycline in eradicating H. pylori infection. METHODS: We comprehensively retrieved the electronic databases of PubMed, Embase, Web of Science, China National Knowledge Infrastructure, SinoMed, and Wanfang database as of October 30, 2023, and finally included 22 research reports on H. pylori eradication with minocycline-containing regimens as per the inclusion and exclusion criteria. The eradication rates of H. pylori were calculated using a fixed or a random effect model, and the heterogeneity and publication bias of the studies were measured. RESULTS: The single-arm meta-analysis revealed that the minocycline-containing regimens achieved good overall H. pylori eradication rates, reaching 82.3% [95% confidence interval (CI): 79.7%-85.1%] in the intention-to-treat analysis and 90.0% (95%CI: 87.7%-92.4%) in the per-protocol analysis. The overall safety and compliance of the minocycline-containing regimens were good, demonstrating an overall incidence of adverse reactions of 36.5% (95%CI: 31.5%-42.2%). Further by traditional meta-analysis, the results showed that the minocycline-containing regimens were not statistically different from other commonly used eradication regimens in eradication rate and incidence of adverse effects. Most of the adverse reactions were mild to moderate and well-tolerated, and dizziness was relatively prominent in the minocycline-containing regimens (16%). CONCLUSION: The minocycline-containing regimens demonstrated good efficacy, safety, and compliance in H. pylori eradication. Minocycline has good potential to replace tetracycline for eradicating H. pylori infection.

An antitumor fungal polysaccharide from Fomitopsis officinalis by activating immunity and inhibiting angiogenesis.

Macrofungi, a class of unique natural resources, are gaining popularity owing to their potential therapeutic benefits and edibility. From Fomitopsis officinalis, a medicinal macrofungus with anticancer activity, a homogeneous heteropolysaccharide (FOBP50-1) with a molecular weight of 2.21 × 104 g/mol has been extracted and purified. FOBP50-1 was found to be composed of 3-O-methylfucose, fucose, mannose, glucose, and galactose with a ratio of 1: 6.5: 4.4: 8.1: 18.2. The sugar fragments and structure of FOBP50-1 were investigated, which included →6)-α-d-Galp-(1→, →2,6)-α-d-Galp-(1→, →3)-α-l-Fucp-(1→, α-d-Glcp-(1→, →3)-ß-d-Manp-(1→, →6)-ß-d-Manp-(1→, 3-O-Me-α-l-Fucp-(1→, according to the UV, FT-IR, GC-MS, and NMR data. Besides the structure elucidation, FOBP50-1 showed promising antitumor activity in the zebrafish assays. The following mechanism examination discovered that FOBP50-1 interacted with TLR-4, PD-1, and VEGF to activate immunity and inhibit angiogenesis according to a series of cell, transgenic zebrafish, and surface plasmon resonance (SPR) experiments. The KD values indicating the association of FOBP50-1 with TLR-4, PD-1, and VEGF, were 4.69 × 10-5, 7.98 × 10-6, 3.04 × 10-6 M, respectively, in the SPR experiments. All investigations have demonstrated that the homogenous fungal polysaccharide FOBP50-1 has the potential to be turned into a tumor immunotherapy agent.

Application of cefuroxime in the eradication therapy of Helicobacter pylori infection: A review article.

BACKGROUND: Helicobacter pylori infection and its associated diseases represent a significant global health concern. Patients who cannot use amoxicillin pose a therapeutic challenge and necessitate alternative medications. Preliminary research indicates that cefuroxime demonstrates promising potential for eradicating H. pylori infection, and there is a lack of comprehensive review articles on the use of cefuroxime. MATERIALS AND METHODS: This study conducts a thorough systematic literature review and synthesis. A comprehensive systematic search was conducted in PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, China Biology Medicine disc, and Wanfang Data up to January 13, 2024. The search strategy utilized the following keywords: (Cefuroxime) AND (Helicobacter pylori OR Helicobacter nemestrinae OR Campylobacter pylori OR Campylobacter pylori subsp. pylori OR Campylobacter pyloridis OR H. pylori OR Hp) for both English and Chinese language publications. Sixteen studies from five different countries or regions were included in final literature review. RESULTS: Analysis results indicate that H. pylori is sensitive to cefuroxime, with resistance rates similar to amoxicillin being relatively low. Regimens containing cefuroxime have shown favorable eradication rates, which were comparable to those of the regimens containing amoxicillin. Regarding safety, the incidence of adverse reactions in cefuroxime-containing eradication regimens was comparable to that of amoxicillin-containing regimens or other bismuth quadruple regimens, with no significant increase in allergic reactions in penicillin-allergic patients. Regarding compliance, studies consistently report high compliance rates for regimens containing cefuroxime. CONCLUSION: Cefuroxime can serve as an alternative to amoxicillin for the patients allergic to penicillin with satisfactory efficacies, safety, and compliance.

Efficacy and safety of intracoronary pro-urokinase combined with low-pressure balloon pre-dilatation during percutaneous coronary intervention in patients with anterior ST-segment elevation myocardial infarction.

BACKGROUND: The efficacy and safety of low-pressure balloon pre-dilatation before intracoronary pro-urokinase (pro-UK) in preventing no-reflow during percutaneous coronary intervention (PCI) remains unknown. This study aimed to evaluate the clinical outcomes of intracoronary pro-UK combined with low-pressure balloon pre-dilatation in patients with anterior ST-segment-elevation myocardial infarction (STEMI). METHODS: This was a randomized, single-blind, investigator-initiated trial that included 179 patients diagnosed with acute anterior STEMI. All patients were eligible for PCI and were randomized into two groups: intracoronary pro-UK combined with (ICPpD group, n = 90) or without (ICP group, n = 89) low-pressure balloon pre-dilatation. The main efficacy endpoint was complete epicardial and myocardial reperfusion. The safety endpoints were major adverse cardiovascular events (MACEs), which were analyzed at 12 months follow-up. RESULTS: Patients in the ICPpD group presented significantly higher TIMI myocardial perfusion grade 3 (TMPG3) compared to those in the ICP group (77.78% versus 68.54%, P = 0.013), and STR ≥ 70% after PCI 30 min (34.44% versus 26.97%, P = 0.047) or after PCI 90 min (40.0% versus 31.46%, P = 0.044). MACEs occurred in 23 patients (25.56%) in the ICPpD group and in 32 patients (35.96%) in the ICP group. There was no difference in hemorrhagic complications during hospitalization between the groups. CONCLUSION: Patients with acute anterior STEMI presented more complete epicardial and myocardial reperfusion with adjunctive low-pressure balloon pre-dilatation before intracoronary pro-UK during PCI. TRIAL REGISTRATION: 2019xkj213.

UAV and Satellite Synergies for Mapping Grassland Aboveground Biomass in Hulunbuir Meadow Steppe.

Aboveground biomass (AGB) is an important indicator of the grassland ecosystem. It can be used to evaluate the grassland productivity and carbon stock. Satellite remote sensing technology is useful for monitoring the dynamic changes in AGB across a wide range of grasslands. However, due to the scale mismatch between satellite observations and ground surveys, significant uncertainties and biases exist in mapping grassland AGB from satellite data. This is also a common problem in low- and medium-resolution satellite remote sensing modeling that has not been effectively solved. The rapid development of uncrewed aerial vehicle (UAV) technology offers a way to solve this problem. In this study, we developed a method with UAV and satellite synergies for estimating grassland AGB that filled the gap between satellite observation and ground surveys and successfully mapped the grassland AGB in the Hulunbuir meadow steppe in the northeast of Inner Mongolia, China. First, based on the UAV hyperspectral data and ground survey data, the UAV-based AGB was estimated using a combination of typical vegetation indices (VIs) and the leaf area index (LAI), a structural parameter. Then, the UAV-based AGB was aggregated as a satellite-scale sample set and used to model satellite-based AGB estimation. At the same time, spatial information was incorporated into the LAI inversion process to minimize the scale bias between UAV and satellite data. Finally, the grassland AGB of the entire experimental area was mapped and analyzed. The results show the following: (1) random forest (RF) had the best performance compared with simple regression (SR), partial least squares regression (PLSR) and back-propagation neural network (BPNN) for UAV-based AGB estimation, with an R2 of 0.80 and an RMSE of 76.03 g/m2. (2) Grassland AGB estimation through introducing LAI achieved higher accuracy. For UAV-based AGB estimation, the R2 was improved by an average of 10% and the RMSE was reduced by an average of 9%. For satellite-based AGB estimation, the R2 was increased from 0.70 to 0.75 and the RMSE was decreased from 78.24 g/m2 to 72.36 g/m2. (3) Based on sample aggregated UAV-based AGB and an LAI map, the accuracy of satellite-based AGB estimation was significantly improved. The R2 was increased from 0.57 to 0.75, and the RMSE was decreased from 99.38 g/m2 to 72.36 g/m2. This suggests that UAVs can bridge the gap between satellite observations and field measurements by providing a sufficient training dataset for model development and AGB estimation from satellite data.

Use of the Serum Level of Cholinesterase as a Prognostic Marker of Nonfatal Clinical Outcomes in Patients Hospitalized with Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Introduction: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) contributes to a poor prognosis. Reliable biomarkers to predict adverse outcomes during hospitalization are important. Aim: To investigate the relationship between the serum cholinesterase (ChE) level and adverse clinical outcomes, including hypoxemia severity, hypercapnia, duration of hospital stay (DoHS), and noninvasive ventilation (NIV) requirement, in patients with AECOPD. Methods: Patients hospitalized with AECOPD in the Wuhu Hospital of Traditional Chinese Medicine between January 2017 and December 2021 were included. Results: A total of 429 patients were enrolled. The serum ChE level was significantly lower in patients with hypercapnia, who required NIV during hospitalization and who had a DoHS of >10 days, with an oxygenation index < 300. The ChE level was correlated negatively with the C-reactive protein level and neutrophil-to-lymphocyte ratio and correlated positively with the serum albumin level. Multivariate logistic regression analysis indicated that a serum ChE level of ≤4116 U/L (OR = 2.857, 95% CI = 1.46-5.58, p = 0.002) was associated significantly with NIV requirement. Conclusions: The serum ChE level was correlated significantly with complicating severe hypoxemia, hypercapnia, prolonged DoHS, and the need for NIV in patients hospitalized with AECOPD. The serum ChE level is a clinically important risk-stratification biomarker in patients hospitalized with AECOPD.

Development and Evaluation of a Quantitative Systems Pharmacology Model for Mechanism Interpretation and Efficacy Prediction of Atezolizumab in Combination with Carboplatin and Nab-Paclitaxel in Patients with Non-Small-Cell Lung Cancer.

Immunotherapy has shown clinical benefit in patients with non-small-cell lung cancer (NSCLC). Due to the limited response of monotherapy, combining immune checkpoint inhibitors (ICIs) and chemotherapy is considered a treatment option for advanced NSCLC. However, the mechanism of combined therapy and the potential patient population that could benefit from combined therapy remain undetermined. Here, we developed an NSCLC model based on the published quantitative systems pharmacology (QSP)-immuno-oncology platform by making necessary adjustments. After calibration and validation, the established QSP model could adequately characterise the biological mechanisms of action of the triple combination of atezolizumab, nab-paclitaxel, and carboplatin in patients with NSCLC, and identify predictive biomarkers for precision dosing. The established model could efficiently characterise the objective response rate and duration of response of the IMpower131 trial, reproducing the efficacy of alternative dosing. Furthermore, CD8+ and CD4+ T cell densities in tumours were found to be significantly related to the response status. This significant extension of the QSP model not only broadens its applicability but also more accurately reflects real-world clinical settings. Importantly, it positions the model as a critical foundation for model-informed drug development and the customisation of treatment plans, especially in the context of combining single-agent ICIs with platinum-doublet chemotherapy.

Solid-State Fermentation Improves Tobacco Leaves Quality via the Screened Bacillus subtilis of Simultaneously Degrading Starch and Protein Ability.

The process of tobacco aging plays a significant role in enhancing the smoking experience by improving the flavor and quality of tobacco leaves. During natural aging, the metabolic activity of the microbes on the surface of tobacco leaves will be greatly changed. Besides, starch and protein are two of the main macromolecular compounds causing the poor smoking quality of tobacco leaves which to be degraded for better tobacco quality. In this study, a bacterium with the simultaneously degrading ability of starch (degradation rate of 33.87%) and protein (degradation rate of 20%) has been screened out from high-class tobacco leaf and then inoculated into low-class tobacco leaf by solid-state fermentation for quality improvement. The changes in components related to carbon and nitrogen showed that the strain had an obvious effect on the quality improvement of tobacco leaves. After that, GC-MS analyses displayed the volatile flavor compounds which become rich and the flavor has been improved. It has been proved that inoculation solid-state fermentation by dominant strain could improve tobacco quality, as well as instead of the traditional natural aging process which greatly shortens the aging process. The work also offers a helpful strategy for solid-state products for deep fermentation.

General anesthesia with endotracheal intubation ensures the quick removal of magnetic foreign bodies: A case report.

BACKGROUND: The incidence of ingestion of magnetic foreign bodies in the gastrointestinal tract has been increasing year by year. Due to their strong magnetic attraction, if multiple gastrointestinal foreign bodies enter the small intestine, it can lead to serious complications such as intestinal perforation, necrosis, torsion, and bleeding. Severe cases require surgical intervention. CASE SUMMARY: We report a 6-year-old child who accidentally swallowed multiple magnetic balls. Under timely and safe anesthesia, the magnetic balls were quickly removed through gastroscopy before entering the small intestine. CONCLUSION: General anesthesia with endotracheal intubation can ensure full anesthesia under the condition of fasting for less than 6 h. In order to prevent magnetic foreign bodies from entering the small intestine, timely and effective measures must be taken to remove the foreign bodies.

Bioinformatics and Systems Biology Approach to Identify the Pathogenetic Link between Heart Failure and Sarcopenia. / Abordagem de Bioinformática e Biologia de Sistemas para Identificar a Ligação Patogenética entre Insuficiência Cardíaca e Sarcopenia.

Despite increasing evidence that patients with heart failure (HF) are susceptible to sarcopenia, the reason for the association is not well understood. The purpose of this study is to explore further the molecular mechanism of the occurrence of this complication. Gene expression datasets for HF (GSE57345) and Sarcopenia (GSE1428) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using 'edgeR' and "limma" packages of R, and their functions were analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein-protein interaction (PPI) networks were constructed and visualized using Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. Hub genes were selected using the plugin cytoHubba and validation with GSE76701 for HF and GSE136344 for Sarcopenia. The related pathways and molecular mechanisms of the hub genes were performed by Gene set enrichment analysis (GSEA). The statistical analyses were performed using R software. P < 0.05 was considered statistically significant. A total of 114 common DEGs were found. Pathways related to growth factor, Insulin secretion and cGMP-PKG were enriched in both HF and Sarcopenia. CYP27A1, KCNJ8, PIK3R5, TIMP2, CXCL12, KIT, and VCAM1 were found to be significant hub genes after validation, with GSEA emphasizing the importance of the hub genes in the regulation of the inflammatory response. Our study reveals that HF and Sarcopenia share common pathways and pathogenic mechanisms. These findings may suggest new directions for future research into the underlying pathogenesis.

Apesar das evidências crescentes de que pacientes com insuficiência cardíaca (IC) são suscetíveis à sarcopenia, o motivo da associação não é bem compreendido. O objetivo deste estudo é explorar ainda mais o mecanismo molecular de ocorrência desta complicação. Conjuntos de dados de expressão gênica para HF (GSE57345) e Sarcopenia (GSE1428) foram obtidos do banco de dados Gene Expression Omnibus (GEO). Genes diferencialmente expressos (DEGs) foram identificados usando pacotes 'edgeR' e "limma" de R, e suas funções foram analisadas usando Gene Ontology (GO) e a Enciclopédia de Genes e Genomas de Kyoto (KEGG). Redes de interação proteína-proteína (PPI) foram construídas e visualizadas usando Search Tool for the Retrieval of Interacting Genes (STRING) e Cytoscape. Os genes hub foram selecionados usando o plugin cytoHubba e validados com GSE76701 para IC e GSE136344 para Sarcopenia. As vias relacionadas e os mecanismos moleculares dos genes hub foram realizados pela análise de enriquecimento de genes (GSEA). As análises estatísticas foram realizadas no software R. P < 0,05 foi considerado estatisticamente significativo. Foram encontrados 114 DEGs comuns. As vias relacionadas ao fator de crescimento, secreção de insulina e cGMP-PKG estavam enriquecidas tanto na IC quanto na sarcopenia. Descobriu-se que CYP27A1, KCNJ8, PIK3R5, TIMP2, CXCL12, KIT e VCAM1 são genes hub significativos após validação com GSEA enfatizando a importância dos genes hub na regulação da resposta inflamatória. Nosso estudo revela que a IC e a Sarcopenia compartilham vias e mecanismos patogênicos comuns. Estes achados podem sugerir novas direções para pesquisas futuras sobre a patogênese subjacente.