Lipid-lowering effects of gefarnate in statin-treated patients with residual hypertriglyceridemia: a randomized controlled study.

BACKGROUND: The prevention of coronary artery disease (CAD) faces dual challenges: the aspirin-induced gastrointestinal injury, and the residual cardiovascular risk after statin treatment. Geraniol acetate (Gefarnate) is an anti-ulcer drug. It was reported that geraniol might participate in lipid metabolism through a variety of pathways. The aim of this study was to assess the lipid-lowering effects of gefarnate in statin-treated CAD patients with residual hypertriglyceridemia. METHODS: In this prospective, open-label, randomized, controlled trial, 69 statin-treated CAD patients with residual hypertriglyceridemia were randomly assigned to gefarnate group and control group, received gefarnate (100 mg/3 times a day) combined with statin and statin alone, respectively. At baseline and after one-month treatment, the levels of plasma triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol were tested. RESULTS: After one-month gefarnate treatment, triglyceride level was significantly lowered from 2.64 mmol/L to 2.12 mmol/L (P = 0.0018), LDL-C level lowered from 2.7 mmol/L to 2.37 mmol/L (P = 0.0004), HDL-C level increased from 0.97 mmol/L to 1.17 mmol/L (P = 0.0228). Based on statin therapy, gefarnate could significantly reduce the plasma triglyceride level (P = 0.0148) and increase the plasma HDL-C level (P = 0.0307). Although the LDL-C and total cholesterol levels tended to decrease, there was no statistically significant difference. CONCLUSIONS: The addition of gefarnate to statin reduced triglyceride level and increased HDL-C level to a significant extent compared to statin alone in CAD patients with residual hypertriglyceridemia. This suggested that gefarnate might provide the dual benefits of preventing gastrointestinal injury and lipid lowering in CAD patients.

Enhancing Anesthesia Education and Clinical Practice: A Comprehensive Review of GASMAN Simulation Software.

GASMAN software, a simulation tool for inhalational anesthetics' pharmacokinetics and pharmacodynamics, has become essential in both anesthesia education and clinical practice. This review explores its applications, highlighting its effectiveness in enhancing medical education and its impact on clinical anesthesia management. In educational settings, GASMAN software facilitates a deeper understanding of anesthetic pharmacology through interactive and visual simulations, thereby improving students' learning outcomes and engagement. Clinically, it aids anesthesiologists in optimizing anesthetic dosing, enhancing patient safety, and supporting real-time decision-making during surgeries. Despite its advantages, GASMAN software faces limitations such as the absence of physiological feedback and the need for continuous data model updates. Future directions include technical enhancements, integration with advanced patient simulators, and broader dissemination through educational partnerships. This review emphasizes the significant contributions of GASMAN software to anesthesia education and clinical practice and suggests pathways for future improvements and wider adoption.

Maduraflavacins A-E, Unusual Phenyl Polyene Metabolites Produced by a Rare Marine-Derived Actinomadura sp.

Phenyl polyenes comprise a small family of bacterial natural products with broad and potent bioactivities, primarily found in actinobacteria. Here we report the discovery of five new phenyl polyene metabolites, maduraflavacins A-E (1-5), from a rare, marine-derived actinobacteria strain Actinomadura glauciflava NA03286. The structures of these natural products were determined by NMR spectroscopy, HRESIMS, LC-MS/MS, and chemical derivatization. All of these new maduraflavacins feature methyl substitutions at the polyene side chain, and maduraflavacins A-C (1-3) possessed a 1-N-ß-d-glucosamine-(3 → 1)-O-ß-d-glucopyranosyl-(3 → 1)-O-ß-d-glucopyranosyl-(6 → 1)-O-ß-d-glucopyranoside tetrasaccharide moiety via an amido linkage with a phenyl polyene skeleton. Compounds 1 and 2 showed weak antibacterial activities against the Gram-positive bacteria Staphylococcus aureus Sau 16339 and Micrococcus luteus, respectively.

Solid-Liquid-Gas Three-Phase Indirect Electrolysis Enabled by Affinity Auxiliary Imparted Covalent Organic Frameworks.

The design of efficient heterogenous redox mediators with favorable affinity to substrate and electrolyte are much desired yet still challenging for the development of indirect electrolysis system. Herein, for the first time, we have developed a solid-liquid-gas three-phase indirect electrolysis system based on a covalent organic framework (Dha-COF-Cu) as heterogenous redox mediator for S-S coupling reaction. Dha-COF-Cu with the integration of high porosity, nanorod morphology, abundant hydroxyl groups and active Cu sites is much beneficial for the adsorption/activation of thiols, uniform dispersion and high wettability in electrolyte, and efficient interfacial electron transfer. Notably, Dha-COF-Cu as solid-phase redox mediator exhibits excellent electrocatalytic efficiency for the formation of value-added liquid-phase S-S bond product (yields up to 99%) coupling with the generation of gas-phase product of H2 (~1.40 mmol g-1 h-1), resulting in a powerful three-phase indirect electrolysis system. This is the first work about COFs that can be applied in three-phase indirect electrolysis system, which might promote the development of porous crystalline materials in this field.

Effect of Different Insertion Methods on LMA Protector-Related Complications: A Prospective Randomized Double-Blind Clinical Trail.

OBJECTIVE: The authors compared the effect of 2 insertion methods, namely the conventional laryngeal mask airway (LMA) insertion and the index finger-assisted LMA insertion, on the incidence of complications associated with LMA Protector insertion. METHODS: The authors enrolled 300 patients, who underwent painless bronchoscopy. The patients ranged in age between 18 and 75 and were classified as American Society of Anesthesiologists grade I to III. They were randomly divided into 2 groups: a control group of 150 patients and an assisted group comprising 150 patients. LMA was inserted using the conventional and index finger-assisted insertion methods in both groups, respectively. The primary outcome was postoperative complications, such as oral mucosal injury and pharyngeal pain. Secondary outcomes included the success rate of first-time insertion, the incidence rate of inverse folding of LMA tips, oropharyngeal leak pressure (OLP), and other postoperative complications. RESULTS: Compared with the conventional LMA insertion method, index finger-assisted LMA insertion can significantly reduce the incidence rate of oral mucosal injury and pharyngeal pain, with fewer insertion failures. There was a statistically significant difference between the 2 groups in the visual field grading before adjustment for LMA alignment (P<0.0001). The conventional insertion method increased the likelihood of inverse folding of LMA tips. When the conventional insertion method was utilized, there was a significant difference in airway pressure and tidal volume before and after alignment under a fiberoptic bronchoscope (P<0.0001), but no significant difference in visual field grading and respiratory mechanics-related indicators. CONCLUSIONS: Index finger-assisted insertion can significantly reduce the incidence rate of LMA Protector-related complications and inverse folding of LMA tips.

Gout or Hyperuricemia and Dementia Risk: A Meta-Analysis of Observational Studies.

Background: As a natural antioxidant, uric acid has neuroprotective effects. The association between uric acid levels and dementia risk was reported by previous studies. However, recently published studies showed that the relationship between uric acid and dementia risk might be heterogeneous in dementia subtypes. Objective: This study aimed to clarify the relationship between hyperuricemia (or gout) and dementia. Methods: The PubMed and Web of Science databases were systematically searched up to April 2024 to identify relevant studies. A meta-analysis was conducted using hazard ratios (HR) or odds ratios (OR) and 95% confidence interval (CI) as pooled indicators. Heterogeneity between the studies was examined using Cochran's Q statistic and I2 statistic. Subgroup analyses were conducted for gender and age. Stratification analysis, sensitivity analyses and meta-regression were conducted to explore possible explanations for heterogeneity. Publication bias was assessed by funnel plot and Egger's test. Results: A total of 11 studies met the inclusion criteria including 2,928,152 participants were abstracted. Hyperuricemia (or gout) did not reduce the overall risk of dementia (OR/HR = 0.92, 95% CI: 0.81-1.05) and vascular dementia (OR/HR = 0.74, 95% CI: 0.53-1.05), but may have a protective effect against Alzheimer's disease (OR/HR = 0.82, 95% CI: 0.70-0.96). Subgroup analysis showed that a lower risk of dementia was observed in men (OR/HR = 0.83, 95% CI: 0.77-0.90) and patients whose age under 65 (OR/HR = 0.83, 95% CI: 0.72-0.95). Conclusions: Patients with gout or hyperuricemia have a low risk of Alzheimer's disease.

Internal Space Modulation of Yolk-Shell FeSe2@Carbon Anode with Peanut-Shaped Morphology Enabling Ultra-Stable and Fast Potassium-Ion Storage.

The poor cycling stability and rate performance of transition metal selenides (TMSs) are caused by their intrinsic low conductivity and poor structural stability, which hinders their application in potassium-ion batteries (PIBs). To address this issue, encapsulating TMSs within carbon nanoshells is considered a viable strategy. However, due to the lack and uncontrollability of internal void space, this structure cannot effectively mitigate the volume expansion induced by large K+, resulting in unsatisfactory electrochemical performance. Herein, peanut-shaped FeSe2@carbon yolk-shell capsules are prepared by modulation of the internal space. The active FeSe2 is encapsulated within a robust carbon shell and an optimal void space is retained between them. The outer carbon shell promotes electronic conductivity and avoids FeSe2 aggregation, while the internal void mitigates volume expansion and effectively ensures the structural integrity of the electrode. Consequently, the FeSe2@carbon anode demonstrates exceptional rate performance (242 mAh g-1 at 10 A g-1) and long cycling stability (350 mAh g-1 after 500 cycles at 1 A g-1). Furthermore, the effect of internal space modulation on electrochemical properties is elucidated. Meanwhile, ex situ characterizations elucidate the K+ storage mechanism. This work provides effective guidance for the design and the internal space modulation of advanced TMSs yolk-shell structures.

CAR-T therapy pulmonary adverse event profile: a pharmacovigilance study based on FAERS database (2017-2023).

Background: Chimeric antigen receptor T-cell (CAR-T) therapy, a rapidly emerging treatment for cancer that has gained momentum since its approval by the FDA in 2017, involves the genetic engineering of patients' T cells to target tumors. Although significant therapeutic benefits have been observed, life-threatening adverse pulmonary events have been reported. Methods: Using SAS 9.4 with MedDRA 26.1, we retrospectively analyzed data from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database, covering the period from 2017 to 2023. The analysis included the Reporting Odds Ratio Proportional Reporting Ratio Information Component and Empirical Bayes Geometric Mean to assess the association between CAR-T cell therapy and adverse pulmonary events (PAEs). Results: The FAERS database recorded 9,400 adverse events (AEs) pertaining to CAR-T therapies, of which 940 (10%) were PAEs. Among these CAR-T cell-related AEs, hypoxia was the most frequently reported (344 cases), followed by respiratory failure (127 cases). Notably, different CAR-T cell treatments demonstrated varying degrees of association with PAEs. Specifically, Tisa-cel was associated with severe events including respiratory failure and hypoxia, whereas Axi-cel was strongly correlated with both hypoxia and tachypnea. Additionally, other CAR-T therapies, namely, Brexu-cel, Liso-cel, Ide-cel, and Cilta-cel, have also been linked to distinct PAEs. Notably, the majority of these PAEs occurred within the first 30 days post-treatment. The fatality rates varied among the different CAR-T therapies, with Tisa-cel exhibiting the highest fatality rate (43.6%), followed by Ide-cel (18.8%). Conclusion: This study comprehensively analyzed the PAEs reported in the FAERS database among recipients of CAR-T cell therapy, revealing conditions such as hypoxia, respiratory failure, pleural effusion, and atelectasis. These CAR-T cell therapy-associated events are clinically significant and merit the attention of clinicians and researchers.

Transcriptome analysis of the aged SAMP8 mouse model of Alzheimer's disease reveals novel molecular targets of formononetin protection.

Background: Senescence-accelerated mouse prone 8 (SAMP8) and age-matched SAMR1 mice are used to study the pathogenesis and therapeutics of Alzheimer's disease (AD); however, the molecular mechanisms are not completely understood. Objective: This study aimed to examine the effects of the 5-month administration of formononetin in SAMP8 mice and used RNA-seq to explore the molecular targets. Methods: SAMP8 mice were orally administered formononetin (0, 8, and 16 mg/kg) from 4 months of age, and age-matched SAMR1 mice were used as controls. Behavioral tests were performed in 9-month-old mice, followed by histopathologic analysis. Total RNA from the hippocampus was isolated and subjected to RNA-seq, RT-qPCR, and bioinformatics analysis. Results: The 9-month-old SAMP8 mice exhibited cognition deficits, evidenced by novel object recognition, open-field test, elevated plus maze, and passive avoidance. Nissl bodies in the cortex and hippocampus were decreased. Formononetin treatments ameliorated behavioral deficits and improved morphological changes, which were evidenced by Nissl and H&E staining. RNA-seq revealed distinct gene expression patterns between SAMP8 and SAMR1 mice. Differentially expressed genes in SAMP8 mice were attenuated or normalized by formononetin. Ingenuity pathway analysis (IPA) of canonical pathway and upstream regulators revealed increases in proinflammatory factors and immune dysfunction and decreases in NRF2 and SIRT-1 signaling pathways, leading to neuroinflammation. Formononetin treatment attenuated or reversed these molecular changes. The transcriptome of SAMP8 mice was correlated with transcriptomic profiles of other AD mouse models in the GEO database. Conclusion: Neuroinflammation and decreased antioxidant and SIRT-1 signaling contributed to cognitive deficits in aged SAMP8 mice, which are potential therapeutic targets of formononetin in combination with other therapies.

[Effect of competition on the prediction accuracy of individual tree biomass model for natural Larix gmelinii forests]. / ç«žäº‰å¯¹å ´å®‰è½å¶æ¾å¤©ç„¶æž—å•æœ¨ç”Ÿç‰©é‡æ¨¡åž‹é¢„ä¼°ç²¾åº¦çš„å½±å“.

Quantifying the impact of competition on individual tree biomass and its distribution pattern can provide a basis for improving the prediction accuracy of forest biomass models. To accurately quantify the effects of competition factors on individual biomass and its distribution, we constructed three different individual biomass models by using nonlinear coupling equations based on the biomass survey data of 50 Larix gmelinii from 18 plots of Pangu Forest Farm in Daxing'an Mountains. M-1 was a traditional singly additive biomass model. M-2 and M-3 were models taking the distance dependent simple competition index (CI) and distance independent relative diameter (Rd) into account, respectively. Those models were used to reveal the influence of competition factors on the prediction accuracy and distribution pattern of single tree biomass model of L. gmelinii. The results showed that the adjusted R2 of three additive models ranged from 0.694 to 0.974, mean prediction errors ranged from -0.017 to 0.021, and mean absolute errors ranged from 0.152 to 0.357. The introduction of Rd could improve the fitting degree and prediction accuracy of most biomass models, but CI did not affect the model fitting effect and prediction ability. Among the three models, M-3 model had the best performance, with good fitting degree and prediction accuracy of the biomass of each part, which could accurately estimate the single tree biomass of L. gmelinii. Further simulation results showed that the variation of biomass with DBH was mainly affected by CI and Rd grade, and the influence of Rd was stronger than CI. CI had greater influence on root and dry biomass, but less influence on branch and leaf biomass. Rd had a more significant effect on biomass of branch and leaf than on that of root and trunk.

Irinotecan plus raltitrexed as second-line treatment in locally advanced or metastatic colorectal cancer patients: a prospective open-label, single-arm, multi-center, phase II study.

BACKGROUND: Colorectal cancer is the third most common cancer and the second leading cause of cancer death. There are limited therapeutic options for the treatment of locally advanced or metastatic colorectal cancers which fail first-line chemotherapy. Phase I/II studies showed that the combined application of the raltitrexed and irinotecan has significant synergistic effect and acceptable toxicity. However, most of these previous studies have relatively small sample size. METHODS: This is a prospective open-label, single-arm, multi-center, Phase II trial. Brief inclusion criteria: patients were aged 18 to 75 years with locally advanced or metastatic colorectal cancer after failure of 5-FU and oxaliplatin therapy. Enrolled patients received raltitrexed (3 mg/m2, d1) and irinotecan (180 mg/m2, d1) each 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, and the secondary endpoints were disease control rate, objective response rate, overall survival and safety. RESULTS: A total of 108 patients were enrolled between September 2016 and May 2020. The median age was 61 years, ECOG 1 score accounts for 67.6%, the rest were ECOG 0. A total of 502 cycles were completed, with an average of 4.6 cycles and a median of 4 cycles. 108 patients were evaluated, with an objective response rate of 17.6%, and disease control rate of 76.9%. The median follow-up time was 27 months (range:3.1-61.0 m) at data cut-off on March 2023. Median progression-free survival was 4.9 months (95% CI 4.1-5.7) and median overall survival was 13.1 months (95% CI 12.2-15.5). The most common adverse events that were elevated are alanine aminotransferase increased, aspartate aminotransferase increased, fatigue, diarrhoea, neutrocytopenia, thrombocytopenia, hypohemoglobin, and leukocytopenia. Most of the adverse events were Grade I/II, which were relieved after symptomatic treatment, and there were no treatment-related cardiotoxicities and deaths. CONCLUSIONS: The combination of raltitrexed and irinotecan as second-line treatment for mCRC could be a reliable option after failure of standard 5-Fu-first-line chemotherapy in locally advanced or metastatic colorectal cancers, especially for patients with 5-FU intolerance (cardiac events or DPD deficiency patients). TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03053167, registration date was 14/2/2017.

Design, Synthesis, Anti-TMV Activity, and Structure-Activity Relationships of Seco-pregnane C21 Steroids and Their Derivatives.

seco-pregnane C21 steroids exhibit high antiviral activity against the tobacco mosaic virus (TMV). However, the structural modification of seco-pregnane C21 steroids and the structure-activity relationship (SAR) of the modified compounds remain unevaluated. Hence, the present study investigated how variations in the original skeletons of natural seco-pregnane C21 steroids affect their antiviral activity. A series of glaucogenin C and A derivatives were designed and synthesized for the first time, and their anti-TMV activity was evaluated. Bioassay results showed that most of the newly designed derivatives exhibited good to excellent antiviral activity; among these derivatives, 5g, 5j, and 5l with higher antiviral activity than that of ningnanmycin emerged as new antiviral candidates. Reverse transcription-polymerase chain reaction and Western blotting assay revealed reduced levels of TMV coat protein (TMV-CP) gene transcription and TMV-CP protein expression, which confirmed the antiviral activity of these derivatives. These compounds also downregulated the expression of NtHsp70-1 and NtHsp70-061. Computational simulations indicated that 5l displayed strong van der Waals energy and electrostatic with the TMV coat protein, affording a lower binding energy (ΔGbind = -56.2 kcal/mol) compared with Ribavirin (ΔGbind = -47.6 kcal/mol). The SAR of these compounds was also evaluated, which demonstrated for the first time that substitutions at C-3 and double bonds of C-5/C-6 and C-13/C-18 are crucial for maintaining high anti-TMV activity.

The Association of HIF-1α/rs2057482 Polymorphism with Idiopathic Scleritis in a Chinese Han Population.

BACKGROUND: To investigate the association of hypoxia-inducible factor-1α (HIF-1α), Janus tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) gene polymorphisms with idiopathic scleritis in a Chinese Han population. METHODS: Ten single nucleotide polymorphisms (SNP) of HIF-1α, tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 3 (STAT3), signal transducer and activator of transcription 4 (STAT4), and retinoid-related orphan nuclear receptors-γ (ROR-γ) were selected for this study. A total of 496 idiopathic scleritis patients and 1009 controls were genotyped by the MassARRAY platform and iPLEX Gold Genotyping Assay. The allele and genotype frequencies were analyzed by Chi-square test and Fisher's exact test. Stratified analyses were performed based on gender and anatomic locations of idiopathic scleritis. RESULTS: The frequencies of CC genotype (p = 6.18 × 10-4, Pc = 0.04, OR = 0.67,95%CI = 0.53-0.84) and C allele (p = 7.08 × 10-4, Pc = 0.04, OR = 0.71,95%CI = 0.58-0.87) for HIF-1α/rs2057482 were found significantly lower in idiopathic scleritis patients when compared to healthy controls. Stratified analysis depending on gender showed significant decreased frequencies of CC genotype (CC: p = 4.04 × 10-4, Pc = 0.02, OR = 0.54, 95%CI = 0.39-0.76) and C allele (C: p = 1.62 × 10-4, Pc = 0.01, OR = 0.58, 95%CI = 0.44-0.77) in male patients. Stratification analysis of rs2057482 according to location of scleritis did not show any significant difference between three subgroups and healthy controls. CONCLUSION: This study showed association between polymorphism of HIF-1α/rs2057482 and susceptibility to idiopathic scleritis in Han Chinese male patients.

Identification of BiP as a temperature sensor mediating temperature-induced germline sex reversal in C. elegans.

Sex determination in animals is not only determined by karyotype but can also be modulated by environmental cues like temperature via unclear transduction mechanisms. Moreover, in contrast to earlier views that sex may exclusively be determined by either karyotype or temperature, recent observations suggest that these factors rather co-regulate sex, posing another mechanistic mystery. Here, we discovered that certain wild-isolated and mutant C. elegans strains displayed genotypic germline sex determination (GGSD), but with a temperature-override mechanism. Further, we found that BiP, an ER chaperone, transduces temperature information into a germline sex-governing signal, thereby enabling the coexistence of GGSD and temperature-dependent germline sex determination (TGSD). At the molecular level, increased ER protein-folding requirements upon increased temperatures lead to BiP sequestration, resulting in ERAD-dependent degradation of the oocyte fate-driving factor, TRA-2, thus promoting male germline fate. Remarkably, experimentally manipulating BiP or TRA-2 expression allows to switch between GGSD and TGSD. Physiologically, TGSD allows C. elegans hermaphrodites to maintain brood size at warmer temperatures. Moreover, BiP can also influence germline sex determination in a different, non-hermaphroditic nematode species. Collectively, our findings identify thermosensitive BiP as a conserved temperature sensor in TGSD, and provide mechanistic insights into the transition between GGSD and TGSD.

[Spatio-temporal Heterogeneity of Factors Influencing Transportation Carbon Emissions in Provinces Along the Belt and Road].

The administrative units of 17 provinces （autonomous regions and municipalities directly under the Central Government） along the "Belt and Road" were selected as basic spatial units to calculate the provincial traffic carbon emissions along the "Belt and Road" from 2000 to 2021. On the basis of analyzing the spatial and temporal characteristics of traffic carbon emissions by using the spatial autocorrelation method, the spatial and temporal heterogeneity of influencing factors of traffic carbon emissions was explored by combining a fixed-effect regression model and geographic detector. The results show that： ① The provincial traffic carbon emissions along the "Belt and Road" had significant spatial positive correlation, and the overall trend was upward. Additionally, the cluster evolution of high and low values of traffic carbon emissions presented the characteristics of polarization in space. The high value cluster area was mainly distributed in the open leading area, and the low value cluster area was mainly distributed in the core area of the silk road. ② Opening-up level and vehicle ownership were the positive driving factors of carbon emissions from transportation, whereas energy intensity, transportation structure, industry development scale, and government intervention were the negative driving factors. ③ Energy intensity and transportation structure were the main driving factors for the spatial variation of transportation carbon emissions, and most of them would produce nonlinear enhancement when they were spatially superimposed with other factors, that is, there was strong synergy among driving factors. The results showed that the provincial traffic carbon emissions along the "Belt and Road" were affected by the surrounding areas, the influence degree was increasing, and there was synergy between the key driving factors of traffic carbon emissions. Therefore, it is suggested that the provinces along the "Belt and Road" should fully consider the spatial and temporal heterogeneity of traffic carbon emission influencing factors and formulate differentiated traffic carbon emission reduction policies.

Network pharmacology and molecular docking analysis predict the mechanisms of Huangbai liniment in treating oral lichen planus.

This study explored the mechanism of Huangbai liniment (HB) for the treatment of oral lichen planus (OLP) through network pharmacology and molecular docking techniques. The study identified HB' active ingredients, therapeutic targets for OLP, and associated signaling pathways. The chemical composition of HB was screened using the HERB database. The disease targets of OLP were obtained through the GeneCards and OMIM databases. A protein-protein interactions network was constructed with the String platform. Topological analysis was performed using Cytoscape software to identify core targets. Gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using the Hiplot database, and the active ingredients and core targets were verified by molecular docking. Date analysis showed that the active composition of HB in the treatment of OLP were quercetin, wogonin, kaempferol, and luteolin. This survey identified 10 potential therapeutic targets, including TNF, CXCL8, IL-6, IL1B, PIK3R1, ESR1, JUN, AKT1, PIK3CA, and CTNNB1. Molecular docking revealed stable interactions between OLP' key targets and HB. These key targets were predominantly involved in the PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, TNF signaling pathway, and HIF-1 signaling pathway. HB plays a crucial role in the treatment of OLP, acting on multiple targets and pathways, particularly the PI3K-Akt signaling pathway. It regulated biological processes like the proliferation of epithelial cells and lymphocytes and mediates the expression of transcription factors, cytokines, and chemokines. Therefore, this study provides a theoretical basis for the clinical trial and application of HB in the therapy of OLP.

Preparation, Characterization and Stability of Calcium-Binding Peptides Derived from Chicken Blood.

Calcium-binding peptides have gained significant attention due to their potential applications in various fields. In this study, we aimed to prepare, characterize, and evaluate the stability of calcium-binding peptides derived from chicken blood. Chicken hemoglobin peptides (CPs) were obtained by protease hydrolysis and were applied to prepare chicken hemoglobin peptide-calcium chelate (CP-Ca). The preparation conditions were optimized, and the characteristics and stability of CP-Ca were analyzed. The optimal chelating conditions were determined by single-factor and response surface tests, and the maximum calcium ion chelating rate was 77.54%. Amino acid analysis indicated that glutamic acid and aspartic acid motifs played an important role in the chelation of the calcium ions and CP. According to the characterization analysis, CP-Ca was a different substance compared with CP; calcium ions chelated CPs via the sites of carbonyl oxygen, carboxyl oxygen, and amino nitrogen groups; and after the chelation, the structure changed from a smooth homogeneous plate to compact granular. The stability analysis showed that CP-Ca was stable at different temperatures, pH, and gastrointestinal conditions. The study indicates that chicken blood is a promising source of peptide-calcium chelates, providing a theoretical basis for application in functional foods and improving the utilization value of chicken blood.

Structural insights into transcription activation of the Streptomyces antibiotic regulatory protein, AfsR.

The Streptomyces antibiotic regulatory proteins (SARPs) are ubiquitously distributed transcription activators in Streptomyces and control antibiotics biosynthesis and morphological differentiation. However, the molecular mechanism behind SARP-dependent transcription initiation remains elusive. We here solve the cryo-EM structure of an AfsR-loading RNA polymerase (RNAP)-promoter intermediate complex (AfsR-RPi) including the Streptomyces coelicolor RNAP, a large SARP member AfsR, and its target promoter DNA that retains the upstream portion straight. The structure reveals that one dimeric N-terminal AfsR-SARP domain (AfsR-SARP) specifically engages with the same face of the AfsR-binding sites by the conserved DNA-binding domains (DBDs), replacing σHrdBR4 to bind the suboptimal -35 element, and shortens the spacer between the -10 and -35 elements. Notably, the AfsR-SARPs also recruit RNAP through extensively interacting with its conserved domains (ß flap, σHrdBR4, and αCTD). Thus, these macromolecular snapshots support a general model and provide valuable clues for SARP-dependent transcription activation in Streptomyces.

Synthesis of Isotypic Giant Polymolybdate Cages for Efficient Photocatalytic C-C Coupling Reactions.

The construction of isotypic high-nuclearity inorganic cages with identical pristine parent structure and increasing nuclearity is highly important for molecular growth and structure-property relationship study, yet it still remains a great challenge. Here, we provide an in situ growth approach for successfully synthesizing a series of new giant hollow polymolybdate dodecahedral cages, Mo250, Mo260-I, and Mo260-E, whose structures are growth based on giant polymolybdate cage Mo240. Remarkably, they show two pathways of nuclear growth based on Mo240, that is, the growth of 10 and 20 Mo centers on the inner and outer surfaces to afford Mo250 and Mo260-I, respectively, and the growth of 10 Mo centers both on the inner and outer surfaces to give Mo260-E. To the best of our knowledge, this is the first study to display the internal and external nuclear growth of a giant hollow polyoxometalate cage. More importantly, regular variations in structure and nuclearity confer these polymolybdate cages with different optical properties, oxidative activities, and hydrogen atom transfer effect, thus allowing them to exhibit moderate to excellent photocatalytic performance in oxidative cross-coupling reactions between different unactivated alkanes and N-heteroarenes. In particular, Mo240 and Mo260-E with better comprehensive abilities can offer the desired coupling product with yield up to 92% within 1 h.

[Proximal femoral nail antirotation combined with locking plate in the treatment of femoral intertrochanteric fractures with lateral wall fractures].

OBJECTIVE: To investigate the effect of locking plate internal fixation for the treatment of proximal lateral femoral wall fracture. METHODS: From January 2021 to June 2022, 31 patients with intertrochanteric fractures and lateral wall fractures were treated. Among them, 15 patients were treated with proximal femoral nail antirotation (PFNA) fixation including 3 males and 12 females with an average age of (75.87±7.46) years old;the other 16 patients were treated with 3.5 mm pre-curved screw locking plate fixtion for lateral wall fracture including 4 males and 12 females with an average age of (76.15±9.47) years old. After surgery, the surgical index, tip-apical distance(TAD), postoperative standing weight-bearing time, and fracture reduction were compared between two groups. Postoperative hip function was evaluated according to Harris hip score. RESULTS: All patients were followed up for an average of (12±5) months ranging from 7 to 17 months. The immediate postoperative neck angle ranged from 111° to 132°(119.3±8.3)°. Fracture reduction results were excellent in 11 cases, fair in 2, worse in 1 in PFNA group;excellent in 12, fair in 3, worse in 1 in PFNA+locking plate group. One case of the PFNA group had a spiral blade cut out through the femoral head. There were significant differences in the time of operation, the amount of blood loss during the operation, the length of incision between two groups(P<0.05). There was no significant difference in TAD and postoperative standing weight-bearing time between two groups(P>0.05). There were significant differences in Harris scores at 6 months after surgery between two groups(P<0.05). CONCLUSION: The application of PFNA-assisted locking plate in the treatment of femoral intertrochanteric fractures with lateral wall fractures is effective, and can restore the integrity of lateral wall, improve the stability of PFNA internal fixation, and reduce postoperative complications.