Efficient Homojunction Tin Perovskite Solar Cells Enabled by Gradient Germanium Doping.

P-type self-doping is known to hamper tin-based perovskites for developing high-performance solar cells by increasing the background current density and carrier recombination processes. In this work, we propose a gradient homojunction structure with germanium doping that generates an internal electric field across the perovskite film to deplete the charge carriers. This structure reduces the dark current density of perovskite by over 2 orders of magnitude and trap density by an order of magnitude. The resultant tin-based perovskite solar cells exhibit a higher power conversion efficiency of 13.3% and excellent stability, maintaining 95% and 85% of their initial efficiencies after 250 min of continuous illumination and 3800 h of storage, respectively. We reveal the homojunction formation mechanism using density functional theory calculations and molecular level characterizations. Our work provides a reliable strategy for controlling the spatial energy levels in tin perovskite films and offers insights into designing intriguing lead-free perovskite optoelectronics.

The effect of konjac glucomannan on enzyme kinetics and fluorescence spectrometry of digestive enzymes: An in vitro research from the perspective of macromolecule crowding.

Konjac glucomannan (KGM) can significantly prolong gastrointestinal digestion. However, it is still worth investigating whether the macromolecular crowding (MMC) induced by KGM is correlated with digestion. In this paper, the MMC effect was quantified by fluorescence resonance energy transfer and microrheology, and the digests of starch, protein, and oil were determined. The digestive enzymes were analyzed by enzyme reaction kinetic and fluorescence quenching. The results showed that higher molecular weight (604.85 âˆ¼ 1002.21 kDa) KGM created a larger MMC (>0.8), and influenced the digestion of macronutrients; the digests of starch, protein, and oil all decreased significantly. MMC induced by KGM decreased the Michaelis-Menten constants (Km and Vmax) of pancreatic α-amylase (PPA), pepsin (PEP), and pancreatic lipase (PPL). The larger MMC (>0.8) induced by KGM resulted in the decrease of fluorescence quenching constants (Ksv) in PPA and PPL, and the increase of Ksv in PEP. Therefore, varying degrees of MMC induced by KGM could play a role in regulating digestion and the inhibitory effect on digestion was more significant in a relatively more crowded environment induced by KGM. This study provides theoretical support for the strategies of nutrient digestion regulation from the perspective of MMC caused by dietary fiber.

In-house ammonia induced lung impairment and oxidative stress of ducks.

Ammonia (NH3) is a toxic gas that in intensive poultry houses, damages the poultry health and induces various diseases. This study investigated the effects of NH3 exposure (0, 15, 30, and 45 ppm) on growth performance, serum biochemical indexes, antioxidative indicators, tracheal and lung impairments in Pekin ducks. A total of 288 one-day-old Pekin male ducks were randomly allocated to 4 groups with 6 replicates and slaughtered after the 21-d test period. Our results showed that 45 ppm NH3 significantly reduced the average daily feed intake (ADFI) of Pekin ducks. Ammonia exposure significantly reduced liver, lung, kidney, and heart indexes, and lowered the relative weight of the ileum. With the increasing of in-house NH3, serum NH3 and uric acid (UA) concentrations of ducks were significantly increased, as well as liver malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPX-Px) contents. High NH3 also induced trachea and lung injury, thereby increasing levels of tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4) in the lung, and decreasing the mRNA expressions of zonula occludens 1 (ZO-1) and claudin 3 (CLDN3) in the lung. In conclusion, in-house NH3 decrease the growth performance in ducks, induce trachea and lung injuries and meanwhile increase the compensatory antioxidant activity for host protection.

Predictive nomogram for lymph node metastasis and survival in gastric cancer using contrast-enhanced computed tomography-based radiomics: a retrospective study.

Background: Lymph node involvement significantly impacts the survival of gastric cancer patients and is a crucial factor in determining the appropriate treatment. This study aimed to evaluate the potential of enhanced computed tomography (CT)-based radiomics in predicting lymph node metastasis (LNM) and survival in patients with gastric cancer before surgery. Methods: Retrospective analysis of clinical data from 192 patients diagnosed with gastric carcinoma was conducted. The patients were randomly divided into a training cohort (n = 128) and a validation cohort (n = 64). Radiomic features of CT images were extracted using the Pyradiomics software platform, and distinctive features were further selected using a Lasso Cox regression model. Features significantly associated with LNM were identified through univariate and multivariate analyses and combined with radiomic scores to create a nomogram model for predicting lymph node involvement before surgery. The predictive performance of radiomics features, CT-reported lymph node status, and the nomogram model for LNM were compared in the training and validation cohorts by plotting receiver operating characteristic (ROC) curves. High-risk and low-risk groups were identified in both cohorts based on the cut-off value of 0.582 within the radiomics evaluation scheme, and survival rates were compared. Results: Seven radiomic features were identified and selected, and patients were stratified into high-risk and low-risk groups using a 0.582 cut-off radiomics score. Univariate and multivariate analyses revealed that radiomics features, diabetes mellitus, Nutrition Risk Screening (NRS) 2002 score, and CT-reported lymph node status were significant predictors of LNM in patients with gastric cancer. A predictive nomogram model was developed by combining these predictors with the radiomics score, which accurately predicted LNM in gastric cancer patients before surgery and outperformed other models in terms of accuracy and sensitivity. The AUC values for the training and validation cohorts were 0.82 and 0.722, respectively. The high-risk and low-risk groups in both the training and validation cohorts showed significant differences in survival rates. Conclusion: The radiomics nomogram, based on contrast-enhanced computed tomography (CECT ), is a promising non-invasive tool for preoperatively predicting LNM in gastric cancer patients and postoperative survival.

Erlotinib combination with a mitochondria-targeted ubiquinone effectively suppresses pancreatic cancer cell survival.

BACKGROUND: Pancreatic cancer is a leading cause of cancer-related deaths. Increased activity of the epidermal growth factor receptor (EGFR) is often observed in pancreatic cancer, and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration. Nevertheless, erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes. We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential (Δψm), facilitate tumor cell uptake of Δψm-sensitive agents, disrupt mitochondrial homeostasis, and subsequently trigger tumor cell death. Erlotinib has not been tested for this effect. AIM: To determine whether erlotinib can elevate Δψm and increase tumor cell uptake of Δψm-sensitive agents, subsequently triggering tumor cell death. METHODS: Δψm-sensitive fluorescent dye was used to determine how erlotinib affects Δψm in pancreatic adenocarcinoma (PDAC) cell lines. The viability of conventional and patient-derived primary PDAC cell lines in 2D- and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone (MitoQ), a Δψm-sensitive MitoQ. The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0. The preclinical efficacy of the two-drug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts. RESULTS: Erlotinib elevated Δψm in PDAC cells, facilitating tumor cell uptake and mitochondrial enrichment of Δψm-sensitive agents. MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses, while erlotinib pretreatment potentiated low doses of MitoQ. SynergyFinder suggested that these drugs synergistically induced tumor cell lethality. Consistent with in vitro data, erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent. CONCLUSION: Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.

Computed tomography-based radiomics nomogram for predicting therapeutic response to neoadjuvant chemotherapy in locally advanced gastric cancer : A scale for treatment predicting.

BACKGROUND AND OBJECTIVE: Neoadjuvant chemotherapy results in various responses when used to treat locally advanced gastric cancer, we aimed to develop and validate a predictive model of the response to neoadjuvant chemotherapy in patients with gastric cancer. METHODS: A total of 128 patients with locally advanced gastric cancer who underwent pre-treatment computed tomography (CT) scanning followed by neoadjuvant chemoradiotherapy were included (training cohort: n = 64; validation cohort: n = 64). We built a radiomics score combined with laboratory parameters to create a nomogram for predicting the efficacy of neoadjuvant chemotherapy and calculating scores for risk factors. RESULTS: The radiomics score system demonstrated good stability and prediction performance for the response to neoadjuvant chemotherapy, with the area under the curve of the training and validation cohorts being 0.8 and 0.64, respectively. The radiomics score proved to be an independent risk factor affecting the efficacy of neoadjuvant chemotherapy. In addition to the radiomics score, four other risk factors were included in the nomogram, namely the platelet-to-lymphocyte ratio, total bilirubin, ALT/AST, and CA199. The model had a C-index of 0.8. CONCLUSIONS: Our results indicated that radiomics features could be potential biomarkers for the early prediction of the response to neoadjuvant treatment.

Modified intratympanic steroid therapy for sudden sensorineural hearing loss via tympanic tube and gelfoam as a salvage treatment.

Background: Sudden sensorineural hearing loss (SSNHL) is a prevalent emergency in ear, nose, and throat practice. Previous studies have demonstrated that intratympanic steroid therapy (IST) can serve as a salvage treatment for SSNHL after the failure of systemic steroid therapy (SST). Objective: This study aimed to analyze the efficacy of modified IST involving the insertion of a tympanic tube and gelfoam as a salvage treatment for patients with SSNHL, and to explore its associated factors. Methods: Totally, 74 patients who were aged 22-81 years with SSNHL were enrolled and allocated to either the control group (n = 25) or the treatment group (n = 49) based on their treatment modalities. All patients received SST lasting for at least 7 days. Subsequently, patients in the treatment group, after SST failure, underwent IST twice a week for 2-6 weeks, while the control group did not. Efficacy was assessed by the improvement in pure tone average at the affected frequency at the beginning and end of IST. Results: Hearing improvement in all patients after IST in the treatment group was 9.71 ± 14.84 dB, with significant improvement at affected frequencies (250-8000 Hz) compared with the control group (P < 0.05). The findings indicated the duration from the onset of SSNHL to the beginning of IST as an independent factor for pure tone average improvement after treatment (P = 0.002), whereas age, duration of SST, and time of IST were not (P > 0.05). Conclusion: The modified IST was demonstrated to be a safe and effective method as a salvage treatment for SSNHL. This study explored the efficacy of a modified IST approach, incorporating the utilization of tympanic tubes and gelfoam as key components. The findings underscore the advantages of gelfoam as a strategic drug carrier placed in the round window niche. By minimizing drug loss, extending action time, and increasing perilymph concentration, gelfoam enhances the therapeutic impact of IST, contributing to improved hearing outcomes in patients with SSNHL.

Manipulating solvent fluidic dynamics for large-area perovskite film-formation and white light-emitting diodes.

Presynthesized perovskite quantum dots are very promising for making films with different compositions, as they decouple crystallization and film-formation processes. However, fabricating large-area uniform films using perovskite quantum dots is still very challenging due to the complex fluidic dynamics of the solvents. Here, we report a robust film-formation approach using an environmental-friendly binary-solvent strategy. Nonbenzene solvents, n-octane and n-hexane, are mixed to manipulate the fluidic and evaporation dynamics of the perovskite quantum dot inks, resulting in balanced Marangoni flow, enhanced ink spreadability, and uniform solute-redistribution. We can therefore blade-coat large-area uniform perovskite films with different compositions using the same fabrication parameters. White and red perovskite light-emitting diodes incorporating blade-coated films exhibit a decent external quantum efficiency of 10.6% and 15.3% (0.04 cm2), and show a uniform emission up to 28 cm2. This work represents a significant step toward the application of perovskite light-emitting diodes in flat panel solid-state lighting.

Boosting Checkpoint Immunotherapy with Biomimetic Nanodrug Delivery Systems.

Immune checkpoint blockade (ICB) has achieved unprecedented progress in tumor immunotherapy by blocking specific immune checkpoint molecules. However, the high biodistribution of the drug prevents it from specifically targeting tumor tissues, leading to immune-related adverse events. Biomimetic nanodrug delivery systems (BNDSs) readily applicable to ICB therapy have been widely developed at the preclinical stage to avoid immune-related adverse events. By exploiting or mimicking complex biological structures, the constructed BNDS as a novel drug delivery system has good biocompatibility and certain tumor-targeting properties. Herein, the latest findings regarding the aforementioned therapies associated with ICB therapy are highlighted. Simultaneously, prospective bioinspired engineering strategies can be designed to overcome the four-level barriers to drug entry into lesion sites. In future clinical translation, BNDS-based ICB combination therapy represents a promising avenue for cancer treatment.

Selpercatinib combination with the mitochondria-targeted antioxidant MitoQ effectively suppresses RET-mutant thyroid cancer.

Genetic alternation of REarranged during Transfection (RET) that leads to constitutive RET activation is a crucial etiological factor for thyroid cancer. RET is known to regulate mitochondrial processes, although the underlying molecular mechanisms remain unclear. We previously showed that the multi-kinase inhibitors vandetanib and cabozantinib increase the mitochondrial membrane potential (Δψm) in RET-mutated thyroid tumor cells and that this effect can be exploited to increase mitochondrial enrichment of Δψm-sensitive agents in the tumor cells. In this study, we hypothesized that the RET-selective inhibitor, selpercatinib, can increase Δψm and, subsequently, tumor cell uptake of the mitochondria-targeted ubiquinone (MitoQ) to the level to break the mitochondrial homeostasis and induce lethal responses in RET-mutated thyroid tumor cells. We show that selpercatinib significantly increased Δψm, and its combination with MitoQ synergistically suppressed RET-mutated human thyroid tumor cells, which we validated using RET-targeted genetic approaches. Selpercatinib and MitoQ, in combination, also suppressed CCDC6-RET fusion cell line xenografts in mice and prolonged animal survival more effectively than single treatments of each agent. Moreover, we treated two patients with CCDC6-RET or RETM918T thyroid cancer, who could not take selpercatinib at regular doses due to adverse effects, with a dose-reduced selpercatinib and MitoQ combination. In response to this combination therapy, both patients showed tumor reduction. The quality of life of one patient significantly improved over a year until the tumor relapsed. This combination of selpercatinib with MitoQ may have therapeutic potential for patients with RET-mutated tumors and intolerant to regular selpercatinib doses.

Ultrathin, ultralight dual-scale fibrous networks with high-infrared transmittance for high-performance, comfortable and sustainable PM0.3 filter.

Highly permeable particulate matter (PM) can carry various bacteria, viruses and toxics and pose a serious threat to public health. Nevertheless, current respirators typically sacrifice their thickness and base weight for high-performance filtration, which inevitably causes wearing discomfort and significant consumption of raw materials. Here, we show a facile yet massive splitting eletrospinning strategy to prepare an ultrathin, ultralight and radiative cooling dual-scale fiber membrane with about 80% infrared transmittance for high-protective, comfortable and sustainable air filter. By tailoring antibacterial surfactant-triggered splitting of charged jets, the dual-scale fibrous filter consisting of continuous nanofibers (44 ± 12 nm) and submicron-fibers (159 ± 32 nm) is formed. It presents ultralow thickness (1.49 µm) and base weight (0.57 g m-2) but superior protective performances (about 99.95% PM0.3 removal, durable antibacterial ability) and wearing comfort of low air resistance, high heat dissipation and moisture permeability. Moreover, the ultralight filter can save over 97% polymers than commercial N95 respirator, enabling itself to be sustainable and economical. This work paves the way for designing advanced and sustainable protective materials.

Association of serum 25-hydroxyvitamin D with bone health measured by calcaneal quantitative ultrasound: a large cross-sectional analysis in children and adolescents.

Background: Vitamin D plays a crucial role in bone health; however, findings in children and adolescents remain inconsistent, and few studies have examined its impact on bone health measured by quantitative ultrasound (QUS). This study aims at assessing the relationship between serum vitamin D levels and bone health, as evaluated by QUS, across varying pubertal stages and genders. Methods: A baseline cross-sectional survey of an ongoing cohort study included 4682 children and adolescents aged 6 to 18 years from Shenzhen, China. Serum levels of 25-hydroxyvitamin D (25(OH)D), which is the sum of 25(OH)D2 and 25(OH)D3, were quantified using liquid chromatography-mass spectrometry. Bone health was measured through calcaneal QUS, utilizing the speed of sound (SOS) in the heel as a principal measure-a higher SOS indicating a denser bone structure. Generalized linear models were used to evaluate the association of serum 25(OH)D, 25(OH)D2, and 25(OH)D3 levels with the SOS. Results: Forty-one point-one percent of this population was vitamin D deficient (serum 25(OH)D < 20 ng ml-1), with only 11.1% being sufficient. In the fully adjusted model, we observed a significant positive association between increased serum 25(OH)D quartiles and SOS. Compared with the participants in the lowest quartiles of serum 25(OH)D, those in successive quartiles of 25(OH)D were 3.54 (95% CI: 0.81, 6.28) m s-1, 5.74 (95% CI: 2.87, 8.61) m s-1, and 8.83 (95% CI: 5.83, 11.84) m s-1, respectively (P for trend < 0.0001). The correlations observed for serum 25(OH)D2 and 25(OH)D3 with SOS were similar to those of serum 25(OH)D. Importantly, this association was primarily observed in post-pubertal children and adolescents but was absent in pre- and mid-pubertal participants (P for interaction = 0.0004). Conclusion: Elevated serum 25(OH)D levels were associated with better bone health, as measured through calcaneal QUS, in children and adolescents, particularly among those who had reached the post-pubertal stage. These findings highlight the crucial importance of maintaining sufficient vitamin D levels to support optimal bone health in this demographic.

Controlled Assembly of a Dawson-like Antimoniotungstate-Supported Trefoil-type Trimer with Good Proton Conductivity Performance.

With the excellent properties of POM in the field of proton conductivity, the preparation of POM-based proton-conductive materials has burst into life. Herein, an unprecedented Sb-templated all-inorganic trimer Na8H18.64[(SbW14O52)3(Sb2W6.12Ru5.88O18)]·85H2O (1), which is based on tetravacant Dawson-like [SbW14O52]17- blocks and exhibits a trefoil type with D3 symmetry, has been successfully designed and synthesized by the assembly of simple materials with a one-pot hydrothermal method under acidic conditions. Also, compound 1 is systematically characterized by single-crystal X-ray diffraction, PXRD, ESI-MS, IR spectroscopy, UV-vis, elemental analysis, and TGA. Crystal structure data analysis demonstrates that compound 1 is constructed by a hexagonal prismatic heterometallic {Sb2W6.12Ru5.88O18} core and three equivalent {SbW14} units bridged through µ2-O atoms in periphery. Subsequently, further property experiments show that compound 1 exhibits high proton conductivity with a conductivity value (σ) of 3.07 × 10-2 S cm-1 at 75 °C and 80% relative humidity (RH). The activation energy of compound 1 evaluated by the Arrhenius plots is 0.22 eV, which indicates that the Grotthuss mechanism is dominant during the process of proton transfer.

The pyroptosis-related signature predicts prognosis and influences the tumor immune microenvironment in dedifferentiated liposarcoma.

Background: Dedifferentiated liposarcoma (DDL), a member of malignant mesenchymal tumors, has a high local recurrence rate and poor prognosis. Pyroptosis, a newly discovered programmed cell death, is tightly connected with the progression and outcome of tumor. Objective: The aim of this study was to explore the role of pyroptosis in DDL. Methods: We obtained the RNA sequencing data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression databases to identify different pyroptosis-related genes (PRGs) expression pattern. An unsupervised method for clustering based on PRGs was performed. Based on the result of cluster analysis, we researched clinical outcomes and immune microenvironment between clusters. The differentially expressed genes (DEGs) between the two clusters were used to develop a prognosis model by the LASSO Cox regression method, followed by the performance of functional enrichment analysis and single-sample gene set enrichment analysis. All of the above results were validated in the Gene Expression Omnibus (GEO) dataset. Results: Forty-one differentially expressed PRGs were found between tumor and normal tissues. A consensus clustering analysis based on PRGs was conducted and classified DDL patients into two clusters. Cluster 2 showed a better outcome, higher immune scores, higher immune cells abundances, and higher expression levels in numerous immune checkpoints. DEGs between clusters were identified. A total of 5 gene signatures was built based on the DEGs and divided all DDL patients of the TCGA cohort into low-risk and high-risk groups. The low-risk group indicates greater inflammatory cell infiltration and better outcome. For external validation, the survival difference and immune landscape between the two risk groups of the GEO cohort were also significant. Receiver operating characteristic curves implied that the risk model could exert its function as an outstanding predictor in predicting DDL patients' prognoses. Conclusion: Our findings revealed the clinical implication and key role in tumor immunity of PRGs in DDL. The risk model is a promising predictive tool that could provide a fundamental basis for future studies and individualized immunotherapy.

Levels of peripheral blood routine, biochemical and coagulation parameters in patients with hemorrhagic fever with renal syndrome and their relationship with prognosis: an observational cohort study.

BACKGROUND: Hantaan virus (HTNV), Seoul virus (SEOV) and Puumala virus (PUUV) are major serotypes of the Hantavirus, which can cause hemorrhagic fever with renal syndrome (HFRS). The pathophysiology of HFRS in humans is complex and the determinants associated with mortality, especially the coagulation and fibrinolysis disorders, are still not been fully elucidated. Severe patients usually manifest multiple complications except for acute kidney injury (AKI). The aim of this study was to observe the levels of peripheral blood routine, biochemical and coagulation parameters during the early stage, so as to find independent risk factors closely related to the prognosis, which may provide theoretical basis for targeted treatment and evaluation. METHODS: A total of 395 HFRS patients from December 2015 to December 2018 were retrospectively enrolled. According to prognosis, they were divided into a survival group (n = 368) and a death group (n = 27). The peripheral blood routine, biochemical and coagulation parameters were compared between the two groups on admission. The relationship between the parameters mentioned above and prognosis was analyzed, and the dynamic changes of the coagulation and fibrinolysis parameters during the first week after admission were further observed. RESULTS: In addition to AKI, liver injury was also common among the enrolled patients. Patients in the death group manifested higher levels of white blood cell counts (WBC) on admission. 27.30% (107/392) of the patients enrolled presented with disseminated intravascular coagulation (DIC) on admission and DIC is more common in the death group; The death patients manifested longer prothrombin time (PT) and activated partial thromboplastin time (APTT), higher D-dimer and fibrinogen degradation product (FDP), and lower levels of platelets (PLT) and fibrinogen (Fib) compared with those of the survival patients. The proportion of D-dimer and FDP abnormalities are higher than PT, APTT and Fib. Prolonged PT, low level of Fib and elevated total bilirubin (TBIL) on admission were considered as independent risk factors for prognosis (death). CONCLUSIONS: Detection of PT, Fib and TBIL on admission is necessary, which might be benefit to early predicting prognosis. It is also important to pay attention to the dynamic coagulation disorders and hyperfibrinolysis during the early stage in the severe HFRS patients.

Rational Design of a Hydrophilic Core-Hydrophobic Shell Yarn-Based Solar Evaporator with an Underwater Aerophilic Surface for Self-Floating and High-Performance Dynamic Water Purification.

Interfacial solar vapor generation holds great promise for alleviating the global freshwater crisis, but its real-world application is limited by the efficiently choppy water evaporation and industrial production capability. Herein, a self-floating solar evaporator with an underwater aerophilic surface is innovatively fabricated by weaving core-shell yarns via mature weaving techniques. The core-shell yarns possess capillary water channels in the hydrophilic cotton core and can trap air in the hydrophobic electrospinning nanofiber shell when submerged underwater, simultaneously realizing controllable water supplies, stable self-flotation, and great thermal insulation. Consequently, the self-floating solar evaporator achieves an evaporation rate of 2.26 kg m-2 h-1 under 1 sun irradiation, with a reduced heat conduction of 70.18 W m-2. Additionally, for the first time, a solar evaporator can operate continuously in water with varying waveforms and intensities over 24 h, exhibiting an outdoor cumulative evaporation rate of 14.17 kg m-2 day-1.

Modified Bushen Yiqi Formula mitigates pulmonary inflammation and airway remodeling by inhibiting neutrophils chemotaxis and IL17 signaling pathway in rats with COPD.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic obstructive pulmonary disease (COPD) is a major global health concern characterized by pulmonary inflammation and airway remodeling. Traditional Chinese medicine, such as Modified Jiawei Bushen Yiqi Formula (MBYF), has been used as a complementary therapy for COPD in China. AIM OF THE STUDY: To investigate the therapeutic potential of MBYF in a rat model of COPD induced by cigarette smoke (CS) exposure and explore the underlying mechanism. MATERIALS AND METHODS: The COPD rat model was established through 24 weeks of CS exposure, with MBYF administration starting in the 9th week. Pulmonary function, histological analysis, inflammatory cell count and molecular assays were employed to assess the effects of MBYF on airway remodeling, pulmonary inflammation, neutrophils chemotaxis and the IL17 signaling pathway. RESULTS: MBYF treatment effectively delayed airway remodeling, as evidenced by improved pulmonary function parameters. Histological examination and bronchoalveolar lavage fluid analysis revealed that MBYF mitigated CS-induced pulmonary inflammation by reducing inflammatory cell infiltration. Pharmacological network analysis suggested that MBYF may act through the IL17 signaling pathway to regulate inflammatory responses. RNA-sequencing and molecular assays indicated that MBYF inhibited neutrophils chemotaxis through downregulating the CXCL1/CXCL5/CXCL8-CXCR2 axis, and suppressed IL17A, IL17F and its downstream cytokines, including IL6, TNFα, IL1ß, and COX2. Furthermore, MBYF inhibited the activation of NF-κB and MAPKs in the IL17 signaling pathway. CONCLUSION: MBYF exhibits potential as an adjunct or alternative treatment for COPD, effectively mitigating CS-induced pulmonary inflammation and airway remodeling through the inhibition of neutrophil chemotaxis and IL17 signaling pathway.

Development and validation of a novel death risk stratification scale in patients with hemorrhagic fever with renal syndrome: a 14-year ambispective cohort study.

OBJECTIVES: To develop and validate a simple and effective death risk stratification scale for hemorrhagic fever with renal syndrome (HFRS). METHODS: In this ambispective cohort study, we investigated the epidemiological and clinical data of 2245 patients with HFRS (1873 enrolled retrospectively and constituting the training cohort, 372 prospectively recruited as the validation cohort) from September 2008 to December 2021, and identified independent risk factors for 30-day death of HFRS. Using logistic regression analysis, a nomogram prediction model was established and was further simplified into a novel scoring scale. Calibration plot, receiver operating characteristic curve, net reclassification index, integrated discrimination index, and decision curve analysis were used to assess the calibration, discrimination, precision, and clinical utility in both training and validation cohorts. RESULTS: Of 2245 patients with HFRS, 132 (5.9%) died during hospitalization. The nomogram prediction model and scoring scale were developed using six predictors: comorbid hypertension, hypotensive shock, hypoxemia, neutrophils, aspartate aminotransferase, and activated partial thromboplastin time. Both the scale and nomogram were well calibrated (near-diagonal calibration curves) and demonstrated significant predictive values (areas under receiver operating characteristic curves >0.9, sensitivity and specificity >90% in the training cohort and >84% in the validation cohort). The simplified scoring scale demonstrated equivalent discriminative ability to the nomogram, with net reclassification index and integrated discrimination index of 0.022 and 0.007 in the training cohort, 0.126 and 0.022 in the validation cohort. Decision curve analysis graphically represented significant clinical utility and comparable net benefits of the nomogram and scoring scale across a range of threshold probabilities. DISCUSSION: This evidence-based, factor-weighted, accurate score could help clinicians swiftly stratify HFRS mortality risk and facilitate the implementation of patient triage and tiered medical services during epidemic peaks.

Size-Dependent Penetration of Nanoparticles in Tumor Spheroids: A Multidimensional and Quantitative Study of Transcellular and Paracellular Pathways.

Tumor penetration of nanoparticles is crucial in nanomedicine, but the mechanisms of tumor penetration are poorly understood. This work presents a multidimensional, quantitative approach to investigate the tissue penetration behavior of nanoparticles, with focuses on the particle size effect on penetration pathways, in an MDA-MB-231 tumor spheroid model using a combination of spectrometry, microscopy, and synchrotron beamline techniques. Quasi-spherical gold nanoparticles of different sizes are synthesized and incubated with 2D and 3D MDA-MB-231 cells and spheroids with or without an energy-dependent cell uptake inhibitor. The distribution and penetration pathways of nanoparticles in spheroids are visualized and quantified by inductively coupled plasma mass spectrometry, two-photon microscopy, and synchrotron X-ray fluorescence microscopy. The results reveal that 15 nm nanoparticles penetrate spheroids mainly through an energy-independent transcellular pathway, while 60 nm nanoparticles penetrate primarily through an energy-dependent transcellular pathway. Meanwhile, 22 nm nanoparticles penetrate through both transcellular and paracellular pathways and they demonstrate the greatest penetration ability in comparison to other two sizes. The multidimensional analytical methodology developed through this work offers a generalizable approach to quantitatively study the tissue penetration of nanoparticles, and the results provide important insights into the designs of nanoparticles with high accumulation at a target site.

Spliceosome component PHD finger 5A is essential for early B lymphopoiesis.

The spliceosome, a multi-megadalton ribonucleoprotein complex, is essential for pre-mRNA splicing in the nucleus and ensuring genomic stability. Its precise and dynamic assembly is pivotal for its function. Spliceosome malfunctions can lead to developmental abnormalities and potentially contribute to tumorigenesis. The specific role of the spliceosome in B cell development is poorly understood. Here, we reveal that the spliceosomal U2 snRNP component PHD finger protein 5A (Phf5a) is vital for early B cell development. Loss of Phf5a results in pronounced defects in B cell development, causing an arrest at the transition from pre-pro-B to early pro-B cell stage in the bone marrow of mutant mice. Phf5a-deficient B cells exhibit impaired immunoglobulin heavy (IgH) chain expression due to defective V-to-DJ gene rearrangement. Mechanistically, our findings suggest that Phf5a facilitates IgH gene rearrangement by regulating the activity of recombination-activating gene endonuclease and influencing chromatin interactions at the Igh locus.