In vivo and in vitro study on the regulatory mechanism of XiaoChaiHu decoction on PANoptosis in sepsis-induced cardiomyopathy.

ETHNOPHARMACOLOGICAL RELEVANCE: In accordance with the tenets of traditional Chinese medicine, sepsis is categorized into three distinct syndromes: heat syndrome, blood stasis syndrome, and deficiency syndrome. Xiaochaihu decoction (XCHD) has many functions, including the capacity to protect the liver, cholagogue, antipyretic, anti-inflammatory, and anti-pathogenic microorganisms. XCHD exerts the effect of clearing heat and reconciling Shaoyang. The XCHD contains many efficacious active ingredients, yet the mechanism of sepsis-induced cardiomyopathy (SIC) remains elusive. AIM OF THE STUDY: To investigate the molecular mechanisms underlying the protective effects of XCHD against SIC using an integrated approach combining network pharmacology and molecular biology techniques. MATERIALS AND METHODS: Network pharmacology methods identified the active ingredients, target proteins, and pathways affected by XCHD in the context of SIC. We conducted in vivo experiments using mice with lipopolysaccharide-induced SIC, evaluating cardiac function through echocardiography and histology. XCHD-containing serum was analyzed to determine its principal active components using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The effects of XCHD-containing serum on SIC were further tested in vitro in LPS-treated H9c2 cardiac cells. Protein expression levels were quantified via Western blotting and enzyme-linked immunosorbent assay (ELISA). Additionally, molecular docking was performed between the active components and ZBP1, a potential target protein. Overexpression of ZBP1 in H9c2 cells allowed for a deeper exploration of its role in modulating SIC-associated gene expression. RESULTS: UPLC-MS/MS identified 31 shared XCHD and XCHD-containing serum components. These included organic acids, terpenoids, and flavonoids, which have been identified as the active components of XCHD. Our findings revealed that XCHD alleviated LPS-induced myocardial injury, improved cardiac function, and preserved cardiomyocyte morphology in mice. In vitro studies, we demonstrated that XCHD-containing serum significantly suppressed the expression of inflammatory cytokines (IL-6, IL-1ß, and TNF-α) in LPS-induced H9c2 cells. Mechanistic investigations showed that XCHD downregulated genes associated with PANoptosis, a novel cell death pathway, suggesting its protective role in sepsis-damaged hearts. Conversely, overexpression of ZBP1 abolished the protective effects of XCHD and amplified PANoptosis-related gene expression. CONCLUSIONS: Our study provides the first evidence supporting the protective effects of XCHD against SIC, both in vitro and in vivo. The underlying mechanism involves the inhibition of ZBP1-initiated PANoptosis, offering new insights into treating SIC using XCHD.

Metrological traceable calibration of organic carbon and elemental carbon based on laboratory-generated reference materials.

Carbonaceous aerosol, including organic carbon (OC) and elemental carbon (EC), has significant influence on human health, air quality and climate change. Accurate measurement of carbonaceous aerosol is essential to reduce the uncertainty of radiative forcing estimation and source apportionment. The accurate separation of OC and EC is controversial due to the charring of OC. Therefore, the development of reference materials (RM) for the validation of OC/EC separation is an important basis for further study. Previous RMs were mainly based on ambient air sampling, which could not provide traceability of OC and EC concentration. To develop traceable RMs with known OC/EC contents, our study applied an improved aerosol generation and mixing technique, providing uniform deposition of particles on quartz filters. To generate OC aerosol with similar pyrolytic property of ambient aerosol, both water soluble organic carbon (WSOC) and water insoluble organic carbon (WIOC) were used, and amorphous carbon was selected for EC surrogate. The RMs were analyzed using different protocols. The homogeneity within the filter was validated, reaching below 2%. The long-term stability of RMs has been validated with RSD ranged from 1.7%-3.2%. Good correlation was observed between nominal concentration of RMs with measured concentration by two protocols, while the difference of EC concentration was within 20%. The results indicated that the newly developed RMs were acceptable for the calibration of OC and EC, which could improve the accuracy of carbonaceous aerosol measurement. Moreover, the laboratory-generated EC-RMs could be suitable for the calibration of equivalent BC concentration by Aethalometers.

Insight into catalytic performance and reaction mechanism for toluene total oxidation over Cu-Ce supported catalyst.

Herein, three supported catalysts, CuO/Al2O3, CeO2/Al2O3, and CuO-CeO2/Al2O3, were synthesized by the convenient impregnation method to reveal the effect of CeO2 addition on catalytic performance and reaction mechanism for toluene oxidation. Compared with CuO/Al2O3, the T50 and T90 (the temperatures at 50% and 90% toluene conversion, respectively) of CuO-CeO2/Al2O3 were reduced by 33 and 39 °C, respectively. N2 adsorption-desorption experiment, XRD, SEM, EDS mapping, Raman, EPR, H2-TPR, O2-TPD, XPS, NH3-TPD, Toluene-TPD, and in-situ DRIFTS were conducted to characterize these catalysts. The excellent catalytic performance of CuO-CeO2/Al2O3 could be attributed to its strong copper-cerium interaction and high oxygen vacancies concentration. Moreover, in-situ DRIFTS proved that CuO-CeO2/Al2O3 promoted the conversion of toluene to benzoate and accelerated the deep degradation path of toluene. This work provided valuable insights into the development of efficient and economical catalysts for volatile organic compounds.

Pregnancy and survival-related outcomes of uveal melanoma treated with brachytherapy in women of reproductive age.

BACKGROUND: To examine if pregnancy affects the prognosis of uveal melanoma (UM) patients undergoing plaque brachytherapy (PBT) and to assess if PBT has any subsequent impact on pregnancy outcomes. METHODS: A retrospective, single-center study was carried out at Beijing Tongren Hospital, focusing on women of childbearing age diagnosed with UM and treated with iodine-125 plaque brachytherapy. Both the outcomes of pregnancies and the health status of the fetuses were monitored. Survival analyses were conducted using the Kaplan-Meier method, with endpoints being metastasis and death. RESULTS: A total of 13 patients who had full-term pregnancies and 96 non-pregnant women matched by age and tumor size were included. The mean follow-up time was 67.0 ± 27.7 months (median:66.0 months, range:21.0 to 116.0 months). In the pregnant group, two patients developed metastases, one of whom died shortly after delivery; local recurrence of UM occurred in 2 patients after or during delivery, and 2 other patients developed secondary glaucoma due to radiation retinopathy. None of the other pregnant patients reported any signs of disease progression. In the control group, 18 metastasis cases including 12 deaths were documented. Pregnant patients and matched control subjects showed no statistical difference in both Metastasis-free survival (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.15-2.86; P = 0.576) and overall survival (HR: 0.48, 95% CI: 0.06-3.66; P = 0.464). All pregnant patients carried the pregnancy to term and delivered healthy children with no report of placental or infant metastases to date. CONCLUSION: Pregnancy does not appear to negatively impact the prognosis of UM patients undergoing PBT. PBT showed no observable detriment to maternal fertility and exhibited no teratogenic effects on the fetus. However, the long-term implications of PBT on pregnancy remain uncertain, necessitating additional, prolonged follow-up studies.

Reducing the risk of unfavourable fractures in Le Fort III osteotomy via a navigation-guided technique.

The aim of this study was to investigate the clinical feasibility of reducing the risk of unfavourable fractures during Le Fort III osteotomy by using a navigation-guided technique. A study was carried out involving 20 patients with Crouzon syndrome treated with Le Fort III osteotomy and distraction osteogenesis from 2018 to 2023 at the International Hospital of Peking University. The Le Fort III osteotomy procedure in experimental group (9 patients) was carried out under the guidance of navigation technique, while in historical control group (11 patients) was carried out by free hand. Immediate postoperative CT scans were acquired within 24h after surgery to observe the osteotomy lines and detect unfavourable fracture lines. There were 4 patients with unfavourable fractures in the navigation group (4/9 = 44%) while 10 patients in the freehand group (10/11 = 91%), with a statistically significant difference in the probability of unfavourable fracture and the number of fracture lines between the two groups (P < 0.05). The difference in unfavourable fracture incidence in the two groups was significant in zygomatic area (P < 0.05) while not significant in mid-palatal area (P > 0.05). And the surgical duration of the navigation group was significantly shorter than that of the freehand group (216 min vs 280 min) (P < 0.05). The above findings suggest that the navigation-guided technique is effective in reducing the risk of unfavourable fractures in Le Fort III osteotomy procedure and decreasing the surgical duration.

A novel blockchain-watermarking mechanism utilizing interplanetary file system and fast walsh hadamard transform.

This article proposes a new digital watermarking mechanism based on the Ethereum blockchain, Smart Contract, and Interplanetary File System (IPFS), with an enhanced Fast Walsh Hadamard Transform (FWHT) algorithm for watermark embedding and extraction. The proposed scheme aims to address the limitations of existing digital watermarking techniques, such as dependence on third-party platforms, by leveraging the decentralization feature of blockchain. The Smart Contract is used to manage the transaction between the parties involved in the watermarking process, while IPFS is used to store the watermark data. The enhanced FWHT algorithm is used to embed the watermark into the host image without affecting its visual quality. The results show that the proposed scheme outperforms the state-of-the-art algorithms in terms of both imperceptibility and robustness. Additionally, it demonstrates that our scheme can effectively resist various attacks. Therefore, our scheme can be a promising solution for image copyright protection, authentication applications, and image trading.

Programmability of dual-color DNA-templated silver nanoclusters for modular design of FRET aptasensors toward multiplexed detection.

By exploiting the programmability of DNA, dual-color DNA-templated silver nanoclusters have been synthesized to serve as a label-free fluorescent probe with a G5-linker at the 3' end. This advancement facilitates the modular design of universal FRET-based aptasensors using aptamers with a C5-linker at the 3' end for multiplexed detection, making them easily switch their applications.

Histone variant H2AZ1 drives lung cancer progression through the RELA-HIF1A-EGFR signaling pathway.

BACKGROUND: A growing body of evidence indicates that histone variants play an oncogenic role in cancer progression. However, the role and mechanism of histone variant H2AZ1 in lung cancer remain poorly understood. In this study, we aim to identify novel functions and molecular mechanisms of H2AZ1 in lung cancer. METHODS: We analyzed H2AZ1 expression in lung adenocarcinoma using several RNA-seq and microarray datasets. Immunohistochemistry staining for H2AZ1 was performed on two sets of lung cancer tissue microarrays. To study the function of H2AZ1, we conducted assays for cell proliferation, colony formation, invasion, and migration. We employed CUT&Tag-seq, ATAC-seq, RNA-seq, and Western blotting to explore the regulatory patterns and potential mechanisms of H2AZ1 in lung adenocarcinoma. RESULTS: Our findings reveal that H2AZ1 is highly expressed in lung cancer and high levels of H2AZ1 mRNA are associated with poor patient survival. Silencing H2AZ1 impaired cell proliferation, colony formation, migration, and invasion. Mechanistically, our CUT&Tag-seq, ATAC-seq, and RNA-seq results showed that H2AZ1 is primarily deposited around TSS and affects multiple oncogenic signaling pathways. Importantly, we uncovered that H2AZ1 may drive lung cancer progression through the RELA-HIF1A-EGFR signaling pathway. CONCLUSION: H2AZ1 plays an oncogenic role via several cancer-related pathways, including the RELA-HIF1A-EGFR axis in lung cancer. Intervention targeting H2AZ1 and its related signaling genes may have translational potential for precision therapy.

Qingxuan Runmu Yin alleviates dry eye disease via inhibition of the HMOX1/HIF-1 pathway affecting ferroptosis.

The prevalence of dry eye disease (DED), a multifactorial ocular surface disease characterized by tear film instability, is increasing yearly. Qingxuan Run Mu Yin (QXRMY) is a traditional Chinese medicine (TCM) consisting of Radix Rehmanniae, Radix Scrophulariae, Rhizoma Atractylodis macrocephalae, Herba Dendrobii, Flos Lonicerae, Forsythia suspensa, Ophiopogon japonicus, Saposhnikovia divaricata, Radix Platycodi, and Radix Glycyrrhizae. It has excellent therapeutic effects on dry eye syndrome and a good anti-inflammatory effect on immune-related inflammation. However, the molecular mechanism of Qing Xuan Run Mu Yin in treating dry eye syndrome is largely unknown. The present study used an online database to identify potential target genes of QXRMY for treating DED. The possible mechanisms of these target genes for the treatment of DED were obtained through Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) databases, Hub genes screened by Cytoscape and intersected with ferroptosis-related genes, and the essential genes were finally obtained based on the results of the analyses. DED cell model and rat model were constructed in this study to validate the critical genes and pathways, and it was confirmed that QXEMY alleviated DED by repressing ferroptosis through inhibiting the HMOX1/HIF-1 pathway. In conclusion, this study integrated network pharmacological analyses and experimental validation to provide an effective method to investigate the molecular mechanism of QXRMY in treating DED.

Quantification and sensitivity assessment of Chinese provincial ecological compensation in the perspective of carbon deficit redistribution.

The ecological compensation mechanism is a tool for managing regional development and promoting the green economy. This paper proposes a revised model for carbon emissions and absorption based on IPCC, then analyses the spatial and temporal variations of carbon emissions, absorption, and deficit in 31 provinces of China from 2001 to 2019. A model was developed to redistribute carbon deficits and compensate for ecological imbalances, with the aim of eliminating background differences between regions. The concept of ecological compensation sensitivity was proposed, and a redundancy analysis (RDA) was conducted to detect possible influencing factors. Results indicate that: (1) The carbon deficits were relatively substantial in the centre and developed coastal regions, which were the subject regions of China's ecological compensation. Meanwhile, the northwest and southwest regions were the object regions of ecological compensation, and the compensated object regions tended to extend towards the southeast. The majority of compensated subject areas are generally less sensitive than compensated object regions. (2) The graph of carbon deficit volume over time shows that China's two carbon targets are closely aligned. The distribution of China's ecological compensation amounts follows the pattern of provincial economic development levels, with higher compensation amounts concentrated in the central and coastal regions. There is a positive correlation between GDP, year, and population size with carbon emission and carbon deficit. Additionally, there is a positive correlation between year, region, and carbon absorption. (3) This compensation model can strongly incentivise the compensation subject area to proactively adjust its economic development model to cope with the significant compensation pressure. Additionally, it can fully encourage the compensation recipient area to continue adhering to the green economic development model. The conclusions of the study hold significant reference value for promoting the development of a green, low-carbon economy.

SCAMPI: A scalable statistical framework for genome-wide interaction testing harnessing cross-trait correlations.

Family-based heritability estimates of complex traits are often considerably larger than their single-nucleotide polymorphism (SNP) heritability estimates. This discrepancy may be due to non-additive effects of genetic variation, including variation that interacts with other genes or environmental factors to influence the trait. Variance-based procedures provide a computationally efficient strategy to screen for SNPs with potential interaction effects without requiring the specification of the interacting variable. While valuable, such variance-based tests consider only a single trait and ignore likely pleiotropy among related traits that, if present, could improve power to detect such interaction effects. To fill this gap, we propose SCAMPI (Scalable Cauchy Aggregate test using Multiple Phenotypes to test Interactions), which screens for variants with interaction effects across multiple traits. SCAMPI is motivated by the observation that SNPs with pleiotropic interaction effects induce genotypic differences in the patterns of correlation among traits. By studying such patterns across genotype categories among multiple traits, we show that SCAMPI has improved performance over traditional univariate variance-based methods. Like those traditional variance-based tests, SCAMPI permits the screening of interaction effects without requiring the specification of the interaction variable and is further computationally scalable to biobank data. We employed SCAMPI to screen for interacting SNPs associated with four lipid-related traits in the UK Biobank and identified multiple gene regions missed by existing univariate variance-based tests. SCAMPI is implemented in software for public use.

Genetic regulation of microRNAs in the older adult brain and their contribution to neuropsychiatric conditions.

MicroRNAs are essential post-transcriptional regulators of gene expression and involved in many biological processes; however, our understanding of their genetic regulation and role in brain illnesses is limited. Here, we mapped brain microRNA expression quantitative trait loci (miR-QTLs) using genome-wide small RNA sequencing profiles from dorsolateral prefrontal cortex (dlPFC) samples of 604 older adult donors of European ancestry. miR-QTLs were identified for 224 miRNAs (48% of 470 tested miRNAs) at false discovery rate < 1%. We found that miR-QTLs were enriched in brain promoters and enhancers, and that intragenic miRNAs often did not share QTLs with their host gene. Additionally, we integrated the brain miR-QTLs with results from 16 GWAS of psychiatric and neurodegenerative diseases using multiple independent integration approaches and identified four miRNAs that contribute to the pathogenesis of bipolar disorder, major depression, post-traumatic stress disorder, schizophrenia, and Parkinson's disease. This study provides novel insights into the contribution of miRNAs to the complex biological networks that link genetic variation to disease.

Association between nighttime sleep duration, nap time, and mild cognitive impairment in Chinese older adults: a cross-sectional study.

OBJECTIVE: This study aims to investigate the relationship between midday nap time, nighttime sleep duration, and mild cognitive impairment (MCI) in Chinese older adults and determine the recommended sleep duration to provide a scientific basis for preventing and managing MCI in this population. METHODS: Utilizing the 2020 China Health and Retirement Longitudinal Study database, the demographic data, health status, and lifestyle information of the study participants were collected. A total of 5,314 valid samples were included in the analysis. Logistic regression and restricted cubic spline plots were employed to explore the relationship between sleep patterns and MCI. RESULTS: In the cross-sectional analysis, a linear relationship was observed between midday nap duration and MCI among Chinese elderly. The probability of MCI was lowest among those who napped for less than 30 min at noon. Compared with individuals who napped for30-90 min, those who did not nap were more likely to have MCI (OR = 1.30, 95% CI: 1.05-1.60). Older adults with napping duration < 30 min (OR = 0.73, 95% CI:0.56-0.95) also exhibited lower probability of MCI when compared those without napping habit, Nighttime sleep duration exhibited a U-shaped relationship with MCI. Individuals with less than approximately 6 h of nighttime sleep showed a gradual decrease in the probability of MCI with increasing sleep duration, whereas those with more than 7.5 h demonstrated an increase in the probability of MCI with longer sleep duration. Older adults who slept less than 6 h at night (OR = 1.22, 95% CI: 1.01 ~ 1.46) or more than 8 h (OR = 1.78, 95% CI: 1.35-2.33) were more likely to develop MCI compared with those who slept 6 to 8 h. CONCLUSION: After controlling for potential confounding variables, both nighttime sleep duration and midday nap duration exhibited a nonlinear "U"-shaped relationship with MCI among the elderly. The probability of depression was lower with a nap duration of approximately 60 min, and the optimal nighttime sleep duration was 6-8 h, with around 7 h providing the greatest cognitive benefits.

High histone H3K18 lactylation level is correlated with poor prognosis in epithelial ovarian cancer.

Protein lactylation has a poor prognosis in malignant tumors, but its impact on the prognosis of epithelial ovarian cancer (EOC) remains unknown. We analyzed 112 patients with EOC. Immunohistochemical staining was used to detect the level of pan lactylation (Pan Kla) and histone H3K18 lactylation (H3K18la) in the EOC tissues and normal ovarian tissues. The result showed that the protein lactylation level in EOC was higher than in normal tissues. Then, we analyzed the relationship between overall survival (OS), progression-free survival (PFS) of EOC, and lactylation. The result showed that patients with high histone H3K18la levels had poorer OS (p=0.028) and PFS (p<0.001). Multivariate Cox regression analysis of PFS showed histone H3K18la was an independent risk factor (p=0.001). In addition, we found that both histone H3K18la and Pan Kla in the cytoplasm were associated with platinum recurrence time (p=0.002/p=0.003). The results also indicated that the H3K18la level was related to a tumor stage (p=0.037). Furthermore, we explored the effects of lactylation on the metastasis of ovarian cancer. The results indicated a significant increase in migration in the promoter group compared to the negative control group and inhibitor group. In conclusion, high histone H3K18la level is associated with poor prognosis in EOC. Protein lactylation may have a significant impact on EOC and could potentially be used as a target for EOC therapy in the future.

Isolation and Characterization of Lytic Bacteriophage vB_KpnP_23: A Promising Antimicrobial Candidate Against Carbapenem-Resistant Klebsiella pneumoniae.

The global health threat posed by carbapenem-resistant Klebsiella pneumoniae (CRKP) is exacerbated by the limited availability of effective treatments. Bacteriophages are promising alternatives to conventional antimicrobial agents. However, current phage databases are limited. Thus, identifying and characterizing new phages could provide biological options for the treatment of multi-drug resistant bacterial infections. Here, we report the characterization of a novel lytic phage, vB_KpnP_23, isolated from hospital sewage. This phage exhibited potent activity against carbapenemase-producing CRKP strains and was characterised by an icosahedral head, a retractable tail, and a genome comprising 40,987 base pairs, with a G+C content of 51%. Capable of targeting and lysing nine different capsule types (K-types) of CRKP, including the clinically relevant ST11-K64, it demonstrated both high bacteriolytic efficiency and stability in various environmental contexts. Crucially, vB_KpnP_23 lacks virulence factors, antimicrobial resistance genes, or tRNA, aligning with the key criteria for therapeutic application. In vitro evaluation of phage-antibiotic combinations revealed a significant synergistic effect between vB_KpnP_23 and meropenem, levofloxacin, or amikacin. This synergy could lead to an 8-fold reduction in the minimum inhibitory concentration (MIC), suggesting that integrated treatments combining this phage with the aforementioned antibiotics may substantially enhance drug effectiveness. This approach not only extends the clinical utility of these antibiotics but also presents a strategic advance in combating antibiotic resistance. Specifically, it underscores the potential of phage-antibiotic combinations as a powerful tool in the treatment of infections caused by CRKP, offering a promising avenue to mitigate the public health challenges of antibiotic-resistant pathogens.

Effectiveness of anti-psychiatric treatment on visual and haptic perceptual disorder for a patient with Alzheimer's disease: A case report.

BACKGROUND: Perception is frequently impaired in patients with Alzheimer's disease (AD). Several patients exhibit visual or haptic hallucinations. CASE SUMMARY: A 71-year-old Chinese man presented with visual and haptic hallucinations he had been experiencing for 2 weeks. The clinical manifestations were the feeling of insects crawling and biting the limbs and geison. He looked for the insects while itching and scratching, which led to skin breakage on the limbs. He was treated with topical and anti-allergic drugs in several dermatology departments without any significant improvement. After admission, the patient was administered risperidone (0.5 mg) and duloxetine (2 mg/day). One week later, the dose of risperidone was increased to 2 mg/day, and that of duloxetine was increased to 60 mg/day. After 2 weeks of treatment, the patient's sensation of insects crawling and biting disappeared, and his mood stabilized. CONCLUSION: This patient manifested psychiatric behavioral symptoms caused by AD brain atrophy. It was important to re-evaluate the patient's cognitive-psychological status when the patient repeatedly went to the hospital for treatment. Follow-up attention to cognitive function and the consideration of perceptual deficits as early manifestations of AD should be considered.

Divergent input patterns to the central lateral amygdala play a duet in fear memory formation.

Somatostatin (SOM)-expressing neurons in the central lateral amygdala (CeL) are responsible for fear memory learning, but the circuit and molecular mechanisms underlying this biology remain elusive. Here, we found that glutamatergic neurons in the lateral parabrachial nucleus (LPB) directly dominated the activity of CeLSOM neurons, and that selectively inhibiting the LPBGlu→CeLSOM pathway suppressed fear memory acquisition. By contrast, inhibiting CeL-projecting glutamatergic neurons in the paraventricular thalamic nucleus (PVT) interfered with consolidation-related processes. Notably, CeLSOM-innervating neurons in the LPB were modulated by presynaptic cannabinoid receptor 1 (CB1R), and knock down of CB1Rs in LPB glutamatergic neurons enhanced excitatory transmission to the CeL and partially rescued the impairment in fear memory induced by CB1R activation in the CeL. Overall, our study reveals the mechanisms by which CeLSOM neurons mediate the formation of fear memories during fear conditioning in mice, which may provide a new direction for the clinical research of fear-related disorders.

Natural Binary Herbal Small Molecules Self-Assembled Nanogel for Synergistic Inhibition of Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is one of the most significant pathogenic infections in childhood, associated with high morbidity and mortality rates. Currently, there is no effective and safe drug or vaccine available for RSV. Glycyrrhizic acid (GA), an active compound derived from the natural herb licorice, has been reported to provide protection against influenza and coronaviruses, exhibiting notable antiviral and anti-inflammatory properties. Ephedrine (EPH) is a commonly prescribed medication for the treatment of cough and asthma, and it also demonstrates certain antiviral effects. In this study, EPH and GA were combined to form an efficient nanomaterial (EPH-GA nanogel). The self-assembly of this nanogel is driven by hydrogen bonding and hydrophobic interactions, allowing it to serve as an antiviral nanomedicine without the need for a dual-component carrier, achieving a 100% drug loading efficiency. Oral administration of the EPH-GA nanogel significantly reduced viral load in the lungs of mice and improved lung lesions and tissue infiltration caused by RSV. Notably, we discovered that the assembled drug may create a "physical barrier" that prevents RSV from adsorbing to host cells, while free GA and EPH may compete with RSV for protein binding sites, thereby enhancing cellular uptake of EPH. Consequently, this prevents RSV infection and proliferation within host cells. Furthermore, the EC50 values changed from 310.83 µM for EPH and 262.88 µM for GA to 68.25 µM for the EPH-GA combination, with a combination index of 0.458. In addition, the in vivo biopharmaceutic process of GA and EPH was investigated, revealing that the oral administration of EPH-GA significantly increased the bioavailability of EPH while maintaining its plasma concentration at a relatively stable level. This enhancement may contribute to a synergistic antiviral effect when combined with GA. Furthermore, the in vivo process of EPH-GA demonstrates the advantage of delivering the drug to the lesion at elevated levels, thereby facilitating its antiviral mechanism at the cellular level. In this study, we identified an effective nanomedicine, EPH-GA nanogel, which can inhibit the proliferation of RSV and mitigate lung lesions resulting from viral infection by influencing the biopharmaceutical process in vivo. This research not only offers a novel strategy for the nanomedicine treatment of RSV but also elucidates, to some extent, the compatibility mechanisms of the multicomponents of traditional Chinese medicine.

Tailoring Li assisted CZTSe film growth under controllable selenium partial pressure and solar cells.

It is still critical to prepare a high-quality absorber layer for high-performance Cu2ZnSnSe4 (CZTSe) multi-component thin film solar cell. The gas pressure during the selenization process is commonly referred to as the pressure of inert gas in the tube furnace, while the exact selenium partial pressure is difficult to be controlled. Therefore, the grain growth under different selenium partial pressures cannot be made clear, and the film quality cannot be controlled as well. In this work, we use a sealed quartz tube as the selenization vessel, which can provide a relatively high and controllable selenium partial pressure during the selenization process. To further tailor the grain growth, lithium doping is also utilized. We find that lithium can greatly promote the growth of CZTSe films as the selenium partial pressure is controlled near the selenium saturation vapor pressure. Combined with ALD-Al2O3, the crystallization quality of CZTSe absorber films is significantly enhanced and the efficiency of CZTSe solar cells achieved a significant improvement. This work clarifies the effect of controllable Se pressure on CZTSe film growth and can lead to better results in CZTSe and other multi-compound thin film solar cells.

Structure-Activity Relationship Studies Leading to the Discovery of Highly Water-Soluble and Biocompatible Acyclic Cucurbit[n]uril FY-3451 as a Universal Antagonist That Rapidly Reverses Neuromuscular Blocking Agents In Vivo.

The development of a reversal agent that can rapidly reverse clinically used nondepolarizing neuromuscular blocking agents (NMBAs) has long been a challenge. Here, we report the synthesis of a series of highly water-soluble acyclic cucurbit[n]urils (acCBs). Systematic structure-activity relationship studies reveal that introducing two propylidene units on the peripheral benzene rings not only remarkably improves the activity of the corresponding derivative acCB6 (FY 3451) in reversing the neuromuscular block of rocuronium, cisatracurium, vecuronium, and pancuronium, the four clinically used NMBAs, through stable inclusion, but also allows for high water-solubility as well as a maximum tolerated dose (2000 mg/kg on rats). In vivo experiments with rats show that, at the identical dose of 25 mg/kg, for rocuronium, vecuronium, and pancuronium, acCB6 can achieve a recovery time shorter than that of sugammadex for rocuronium and, at the dose of 100 mg/kg, realize comparably rapid reversal for cisatracurium.