The mechanism of Xihuang pills' intervention in the tumour immune microenvironment for the treatment of liver cancer based on the STAT3-PDL1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xihuang pills, a time-honored Chinese compound formula with a history spanning thousands of years, have demonstrated remarkable efficacy in treating various cancers, such as breast cancer, colon cancer, and liver cancer. Clinical applications over the years have established their effectiveness. Several scholars conducting experimental studies have elucidated the potent tumor-suppressing effects of Xihuang pills. While the inhibition of tumor vascular development and prevention of tumor cell invasion and metastasis have been well-explored mechanisms, the impact on the tumor immune microenvironment has received less attention. This study focuses on investigating the immune microenvironment adjustments induced by Xihuang pills in hepatocellular carcinoma. AIM OF THE STUDY: Tumour cells will find an escape phenomenon during tumour immunotherapy, which will affect immunotherapy results. We will research the regulation of the tumour immune microenvironment, to provide a more complete and precise basis for the elucidation of the mechanism of Xihuang pills in treating cancers. It provides new research ideas for people to treat liver cancer. MATERIALS AND METHODS: Through in vivo and in vitro assessments confirming the intervention effects of Xihuang pills, we observed alterations in T cell typing, macrophage polarization, and tumor-associated cytokine levels. The primary active ingredients of Xihuang pills were identified using UPLC-MS/GC-MS, and relevant pathways in the treatment of hepatocellular carcinoma were predicted through network pharmacology. Combining the network pharmacology approach, we predicted the pathways relevant to Xihuang pills in treating hepatocellular carcinoma and experimentally validated the involvement of PD-1/PD-L1, a key immunity-related axis. RESULTS: Xihuang Pill has a regulatory effect on the tumor immune microenvironment. CONCLUSIONS: The results indicated that Xihuang pills could impact splenic lymphocyte phenotyping, macrophage polarization, and IL-6 cytokine expression in liver cancer mice. The mechanism of action was associated with the regulation of the PD-1/PD-L1 signaling pathway by the STAT3 protein.

Emerging non-antibody‒drug conjugates (non-ADCs) therapeutics of toxins for cancer treatment.

The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins. In recent years, toxins have been widely used as warheads for antibody‒drug conjugates (ADCs) due to their efficient killing activity against various cancer cells. Although ADCs confer certain targeting properties to the toxins, low drug loading capacity, possible immunogenicity, and other drawbacks also limit the potential application of ADCs. Recently, non-ADC delivery strategies for toxins have been extensively investigated. To further understand the application of toxins in anti-tumor, this paper provided an overview of prodrugs, nanodrug delivery systems, and biomimetic drug delivery systems. In addition, toxins and their combination strategies with other therapies were discussed. Finally, the prospect and challenge of toxins in cancer treatment were also summarized.

Microenvironmental Enzyme-Responsive Methotrexate Modified Quercetin Micelles for the Treatment of Rheumatoid Arthritis.

Purpose: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease involving synovial inflammation and joint destruction. Although therapeutic drugs for RA have some efficacy, they usually cause severe side effects and are expensive. RA is characterized by synovial hyperplasia, intra-articular hypoxia, upregulated expression of matrix metalloproteinases, and excessive accumulation of reactive oxygen species. The adverse microenvironment further aggravates activated macrophage infiltration. Therefore, controlling the microenvironment of diseased tissues and targeting the activated macrophages have become new therapeutic targets in RA patients. Methods: Here, microenvironment-targeting micelles (PVGLIG-MTX-Que-Ms) were synthesized using the thin film hydration method. In the inflammatory microenvironment, PVGLIG was cleaved by the highly expressed MMP-2, PEG5000 was eliminated, MTX was exposed, macrophage activation was targeted, and Que enrichment was enhanced. The cytotoxicity, targeting, antioxidant, and anti-inflammatory properties of drug-loaded micelles were tested in vitro. The drug-loaded micelles were used to treat CIA rats. In vivo targeting, expression of serum inflammatory factors, immunohistochemistry of the articular cartilage, and changes in immunofluorescence staining were observed. Results: The developed micelles had a particle size of (89.62 ±1.33) nm and a zeta potential of (-4.9 ±0.53) mV. The IC50 value of PVGLIG-MTX-Que-Ms (185.90 ±6.98) µmol/L was significantly lower than that of free Que (141.10 ±6.39) µmol/L. The synthesized micelles exhibited slow-release properties, low cytotoxicity, strong targeting abilities, and significant anti-inflammatory effects in vitro. In vivo, the drug-loaded micelles accumulated at the joint site for a long time. PVGLIG-MTX-Que-Ms significantly reduced joint swelling, improved bone destruction, and decreased the expression of serum inflammatory factors in CIA rats. Conclusion: The smart-targeting micelles PVGLIG-MTX-Que-Ms with strong targeting, anti-inflammatory, cartilage-protective, and other multiple positive effects are a promising new tool for RA treatment.

Resilience provides mediating effect of resilience between fear of progression and sleep quality in patients with hematological malignancies.

BACKGROUND: Hematological tumors are common malignant tumors, with high morbidity and mortality rates. Most patients with hematological malignancies develop sleep disorders that seriously affect their life and health because of acute onset of disease, rapid progression, high recurrence rates, complex treatment methods, and treatment costs. AIM: To explore the mediating effect of resilience on fear of disease progression and sleep quality in patients with hematological malignancies. METHODS: A cross-sectional analysis of 100 patients with hematological malignancies, treated in the First Affiliated Hospital of Jinzhou Medical University between August 2022 and August 2023, was conducted. Patients were assessed using a general data survey, a simplified scale for the fear of progression (FoP) of disease, a resilience scale, and the Pittsburgh Sleep Quality Index. Statistical analysis was conducted to determine the relationship between various patient characteristics and FoP, resilience, and sleep quality. Spearman's correlation analysis was used to examine the correlations between mental resilience, FoP, and sleep quality. RESULTS: The total FoP score mean value in patients with hematological malignancies was 38.09 ± 5.16; the total resilience score mean value was 40.73 ± 7.04; and the Pittsburgh Sleep Quality Index score mean value was 10.72 ± 1.90. FoP, resilience, and sleep quality of the patients were associated with family per capita monthly income and patient education level (P < 0.05). Spearman correlation analysis revealed that FoP was negatively correlated with resilience and sleep quality scores (r = -0.560, -0.537, P < 0.01), respectively, and resilience was significantly associated with sleep quality scores (r = 0.688, P < 0.01). Mediation analysis showed that the mediating effect of resilience between FoP and sleep quality in patients with hematological malignancies was -0.100 and accounted for 50.51% of the total effect. This indicated that FoP directly and indirectly affected sleep quality through the mesomeric effect of resilience. CONCLUSION: Resilience is an intermediary variable between FoP and sleep quality in patients with hematological malignancies. Medical staff should evaluate and follow-up FoP and resilience to implement measures to improve sleep quality.

The therapeutic potential of Ziziphi Spinosae Semen and Polygalae Radix in insomnia management: Insights from gut microbiota and serum metabolomics techniques.

ETHNOPHARMACOLOGICAL RELEVANCE: Ziziphi Spinosae Semen and Polygalae Radix (ZSS-PR) constitute a traditional Chinese herbal combination with notable applications in clinical and experimental settings due to their evident sedative and calming effects. Aligned with traditional Chinese medicine principles, Ziziphi Spinosae Semen supports cardiovascular health, nourishes the liver, and induces mental tranquillity. Simultaneously, Polygalae Radix elicits calming effects, fosters clear thinking, and reinstates proper coordination between the heart and kidneys. ZSS-PR is commonly employed as a therapeutic intervention for various insomnia types, demonstrating distinct clinical efficacy. Our previous study findings provide evidence that ZSS-PR administration significantly reduces sleep onset latency, increases overall sleep duration, and improves abnormal neurotransmitter levels in a murine insomnia model. AIM OF STUDY: This investigation aimed to scrutinize the intrinsic regulatory mechanism of ZSS-PR in managing insomnia using gut microbiota and serum metabolomics techniques. MATERIALS AND METHODS: Mice were given DL-4-Chlorophenylalanine to induce insomnia and then treated with ZSS-PR. The open-field test assessed the animals' spontaneous activity. Concentrations of neurotransmitters, endocrine hormones, and cytokines in the duodenum were measured using enzyme linked immunosorbent assay, and brain histopathology was evaluated with H&E staining. The impact of ZSS-PR on the metabolic profile was examined by liquid chromatography couped to high resolution mass spectrometry, and 16S rDNA sequencing was used to study the influence of ZSS-PR on the gut microbiota. Additionally, the content of short-chain fatty acids (SCFAs) was analyzed by GC-MS. Finally, correlation analysis investigated relationships between biochemical markers, metabolites, SCFAs, and gut microbiota. RESULTS: ZSS-PR treatment significantly increased movement time and distance in mice with insomnia and improved pathological impairments in the cerebral cortex and hippocampus. It also restored abnormal levels of biochemical markers in the gut of insomnia-afflicted mice, including 5-hydroxytryptamine, dopamine, gastrin, melatonin, tumour necrosis factor-α, and interleukin-1ß. Metabolomics findings showed that ZSS-PR had a significant restorative effect on 15 endogenous metabolites in mice with insomnia. Furthermore, ZSS-PR primarily influenced five metabolic pathways, such as phenylalanine, tyrosine, and tryptophan biosynthesis, glutamine, and glutamate metabolism. Additionally, gut microbiota analysis revealed notable alterations in both diversity and microbial composition after ZSS-PR treatment. These changes were primarily attributed to the relative abundances of microbiota, including Firmicutes, Bacteroidota, Fusobacteriota, Muribaculaceae_unclassified, and Ligilactobacillus. The results of SCFAs analysis demonstrated that ZSS-PR effectively restored abnormal levels of acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid, and valeric acid in insomniac mice. Subsequent correlation analysis revealed that microbiota show obvious correlations with both biochemical markers and metabolites. CONCLUSIONS: The results provide compelling evidence that ZSS-PR effectively mitigates abnormal activity, reduces cerebral pathological changes, and restores abnormal levels of neurotransmitters, endocrine hormones, and cytokines in mice with insomnia. The underlying mechanism is intricately linked to the modulation of gut microbiota and endogenous metabolic pathways.

Glycosides constituents from Codonopsis pilosula.

A new glycoside (1) along with six known analogues (1-7) were isolated from Codonopsis pilosula collected at Shanxi in China. The structure of 1 was established based on comprehensive spectroscopic data and literature comparison. The anti-inflammatory effects of isolated compounds were further investigated in LPS-induced RAW264.7 macrophage.

Fe-MOF/AuNP-based ratiometric electrochemical immunosensor for the detection of deoxynivalenol in grain products.

A ratiometric assay was designed to improve the sensitivity and reliability of electrochemical immunosensors for deoxynivalenol (DON) detection. The indicator signal caused by the Fe-based metal-organic framework nanocomposites loaded with gold nanoparticles and the internal reference signal from the [Fe(CN)6]3-/4- in the electrolyte came together at the immunosensor. When immunoreactivity occurred, the indicator signals decreased as the concentration of DON increased, while the internal reference signals increased slightly. The ratio of the indicator signal to the internal reference signal was available for reproducible and sensitive monitoring of DON. The prepared immunosensor showed excellent performance in the range from 0.5 to 5000 pg mL-1, and the detection limit was 0.0166 pg mL-1. The immunosensor achieved satisfactory detection toward DON in spiked and actual samples and has a promising application in the control of DON in grain products.

Mechanistic insights into the interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins.

TAX1BP1, a multifunctional autophagy adaptor, plays critical roles in different autophagy processes. As an autophagy receptor, TAX1BP1 can interact with RB1CC1, NAP1, and mammalian ATG8 family proteins to drive selective autophagy for relevant substrates. However, the mechanistic bases underpinning the specific interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins remain elusive. Here, we find that there are two distinct binding sites between TAX1BP1 and RB1CC1. In addition to the previously reported TAX1BP1 SKICH (skeletal muscle and kidney enriched inositol phosphatase (SKIP) carboxyl homology)/RB1CC1 coiled-coil interaction, the first coiled-coil domain of TAX1BP1 can directly bind to the extreme C-terminal coiled-coil and Claw region of RB1CC1. We determine the crystal structure of the TAX1BP1 SKICH/RB1CC1 coiled-coil complex and unravel the detailed binding mechanism of TAX1BP1 SKICH with RB1CC1. Moreover, we demonstrate that RB1CC1 and NAP1 are competitive in binding to the TAX1BP1 SKICH domain, but the presence of NAP1's FIP200-interacting region (FIR) motif can stabilize the ternary TAX1BP1/NAP1/RB1CC1 complex formation. Finally, we elucidate the molecular mechanism governing the selective interactions of TAX1BP1 with ATG8 family members by solving the structure of GABARAP in complex with the non-canonical LIR (LC3-interacting region) motif of TAX1BP1, which unveils a unique binding mode between LIR and ATG8 family protein. Collectively, our findings provide mechanistic insights into the interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins and are valuable for further understanding the working mode and function of TAX1BP1 in autophagy.

Integrating shear wave elastography and estimated glomerular filtration rate to enhance diagnostic strategy for renal fibrosis assessment in chronic kidney disease.

Background: Assessing renal fibrosis non-invasively in patients with chronic kidney disease (CKD) remains a considerable clinical challenge. This study aimed to investigate the diagnostic efficacy of different approaches that combine shear wave elastography (SWE) and estimated glomerular filtration rate (eGFR) in distinguishing between mild fibrosis and moderate-to-severe fibrosis in CKD patients. Methods: In this prospective study, 162 patients underwent renal SWE examinations and renal biopsies. Using SWE, the right renal cortex stiffness was measured, and the corresponding SWE value was recorded. Four diagnostic patterns were used to combine eGFR and SWE value: in isolation, in series, in parallel, and in integration. The receiver operating characteristic (ROC) curve was established, and the area under the ROC curve (AUC) was calculated to quantify diagnostic performance. Sensitivity, specificity, and accuracy were computed. Results: The eGFR demonstrated sensitivity of 68.2% and specificity of 83.8%, whereas the SWE value displayed sensitivity of 84.1% and specificity of 62.2%, yielding a similar AUC (78.2% and 77.8%, respectively). Combining in series improved specificity to 97.3%, superior to other diagnostic patterns (all P values <0.01), but compromised sensitivity to 58.0%. When combined in parallel, the sensitivity increased to 94.3%, exceeding any other strategies (all P values <0.05), but the specificity dropped to 48.7%. The integrated strategy, incorporating eGFR with SWE value via the logistic regression algorithm, exhibited an AUC of 85.8%, outperforming all existing approaches (all P values <0.01), with balanced sensitivity, specificity, and accuracy of 86.4%, 74.3%, and 80.9%, respectively. Conclusions: Using an integrated strategy to combine eGFR and SWE value could improve diagnostic performance in distinguishing between mild renal fibrosis and moderate-to-severe renal fibrosis in patients with CKD, thereby helping clinicians perform a more accurate clinical diagnosis.

Interpretable machine learning model integrating clinical and elastosonographic features to detect renal fibrosis in Asian patients with chronic kidney disease.

BACKGROUND: Non-invasive renal fibrosis assessment is critical for tailoring personalized decision-making and managing follow-up in patients with chronic kidney disease (CKD). We aimed to exploit machine learning algorithms using clinical and elastosonographic features to distinguish moderate-severe fibrosis from mild fibrosis among CKD patients. METHODS: A total of 162 patients with CKD who underwent shear wave elastography examinations and renal biopsies at our institution were prospectively enrolled. Four classifiers using machine learning algorithms, including eXtreme Gradient Boosting (XGBoost), Support Vector Machine (SVM), Light Gradient Boosting Machine (LightGBM), and K-Nearest Neighbor (KNN), which integrated elastosonographic features and clinical characteristics, were established to differentiate moderate-severe renal fibrosis from mild forms. The area under the receiver operating characteristic curve (AUC) and average precision were employed to compare the performance of constructed models, and the SHapley Additive exPlanations (SHAP) strategy was used to visualize and interpret the model output. RESULTS: The XGBoost model outperformed the other developed machine learning models, demonstrating optimal diagnostic performance in both the primary (AUC = 0.97, 95% confidence level (CI) 0.94-0.99; average precision = 0.97, 95% CI 0.97-0.98) and five-fold cross-validation (AUC = 0.85, 95% CI 0.73-0.98; average precision = 0.90, 95% CI 0.86-0.93) datasets. The SHAP approach provided visual interpretation for XGBoost, highlighting the features' impact on the diagnostic process, wherein the estimated glomerular filtration rate provided the largest contribution to the model output, followed by the elastic modulus, then renal length, renal resistive index, and hypertension. CONCLUSION: This study proposed an XGBoost model for distinguishing moderate-severe renal fibrosis from mild forms in CKD patients, which could be used to assist clinicians in decision-making and follow-up strategies. Moreover, the SHAP algorithm makes it feasible to visualize and interpret the feature processing and diagnostic processes of the model output.

Association of renal elasticity evaluated by real-time shear wave elastography with renal fibrosis in patients with chronic kidney disease.

OBJECTIVE: Renal fibrosis is a final common pathological hallmark in the progression of chronic kidney disease (CKD). Non-invasive evaluation of renal fibrosis by mapping renal stiffness obtained by shear wave elastography (SWE) may facilitate the clinical therapeutic regimen for CKD patients. METHODS: A cohort of 162 patients diagnosed with CKD, who underwent renal biopsy, was prospectively and consecutively recruited between April 2019 and December 2021. The assessment of renal cortex stiffness was performed using SWE imaging. The patients were classified into different groups based on pathological renal fibrosis (mild group: n = 74; moderate-to-severe group: n = 88). Binary logistic regression model and generalized additive model were conducted to investigate the association of renal elasticity with renal fibrosis. RESULTS: Compared with the mildly impaired group, the moderate-to-severe group showed a significant decline in renal elasticity (P < .001). In the fully adjusted model, each 10 kPa drop in renal elasticity was associated with a 3.5-fold increment in the risk of moderate-to-severe renal fibrosis (fully adjusted odds ratio, 4.54; 95% CI, 2.41-8.57). Particularly, participants in the lowest elasticity group (≤29.92 kPa) had a 20-fold increased chance of moderate-to-severe renal fibrosis than those in the group with highest elasticity (≥37.93 kPa). An inverse linear association was observed between renal elasticity increment and moderate-to-severe renal fibrosis risk. CONCLUSION: There is a negative linear association between increased renal elasticity and moderate-to-severe renal fibrosis risk among CKD patients. Patients with diminished renal stiffness have a higher risk of moderate-to-severe renal fibrosis. ADVANCES IN KNOWLEDGE: CKD patients with reduced renal stiffness have a higher likelihood of moderate-to-severe renal fibrosis.

Influencing factors of cancer-related fatigue in acute leukemia patients: A cross-sectional study.

Purpose: To investigate influencing factors of cancer-related fatigue (CRF) in adult patients with acute leukemia (AL). Methods: A total of 288 adult patients diagnosed with acute leukemia in West China Hospital were included in this study. A cross-sectional survey, including the Clinical Information Questionnaire, the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Pittsburgh Sleep Quality Index (PSQI), and Hospital Anxiety and Depression Scale (HAD), was provided to the patients. Hierarchical multiple linear regression analyses were conducted to evaluate the associations of the variable factors and the AL patients' CRF. Results: The CRF score of AL patients was 33.25 ± 10.35. Gender, age, albumin level, depression, anxiety status of the patients and treatment cycles were identified as influencing factors of CRF in AL patients (P < 0.05). The CRF level of acute leukemia patients in the complete remission group was lower than that of patients who were not achieving complete remission. Depression, anxiety, age, employment, albumin, and sleep disturbance were independent influencing factors for CRF in patients who were not achieving complete remission. Conclusions: Acute leukemia patients who are female, older, hypoalbuminemia，or in the induction therapy have a higher risk of developing a high degree of CRF. Clinical staff should pay more attention to the CRF of patients who were not achieving complete remission. Early screening and aggressive intervention could be adopted in caring for these patients.

Mechanistic insights into the homo-dimerization of HOIL-1L and SHARPIN.

HOIL-1L and SHARPIN are two essential regulatory subunits of the linear ubiquitin chain assembly complex (LUBAC), which is the only known E3 ligase complex generating linear ubiquitin chains. In addition to their LUBAC-dependent functions, HOIL-1L and SHARPIN alone play crucial roles in many LUBAC-independent cellular processes. Importantly, deficiency of HOIL-1L or SHARPIN leads to severe disorders in humans or mice. However, the mechanistic bases underlying the multi-functions of HOIL-1L and SHARPIN are still largely unknown. Here, we uncover that HOIL-1L and SHARPIN alone can form homo-dimers through their LTM motifs. We solve two crystal structures of the dimeric LTM motifs of HOIL-1L and SHARPIN, which not only elucidate the detailed molecular mechanism underpinning the dimer formations of HOIL-1L and SHARPIN, but also reveal a general mode shared by the LTM motifs of HOIL-1L and SHARPIN for forming homo-dimer or hetero-dimer. Furthermore, we elucidate that the polyglucosan body myopathy-associated HOIL-1L A18P mutation disturbs the structural folding of HOIL-1L LTM, and disrupts the dimer formation of HOIL-1L. In summary, our study provides mechanistic insights into the homo-dimerization of HOIL-1L and SHARPIN mediated by their LTM motifs, and expands our understandings of the multi-functions of HOIL-1L and SHARPIN as well as the etiology of relevant human disease caused by defective HOIL-1L.

Study of self-assembling properties of HBc-VLP derivatives aided by molecular dynamic simulations from a thermodynamic perspective.

Self-assembling protein nanoparticles showed promise for vaccine design due to efficient antigen presentations and safety. However, the unpredictable formations of epitopes-fused protein assemblies remain challenging in the upstream design. This study suggests employing molecular dynamic (MD) simulations to investigate the assembly properties of Hepatitis B core protein (HBc) from thermodynamic perspectives. Eight HBc derivatives were expressed in E. coli, with their self-assembly properties characterised by high-performance liquid chromatography and transmission electron microscopy. MD simulations on the dimers, based on AlphaFold-predicted 3D structures, analysed the derivative at the atomic level. Results revealed that HBc derivatives can form dissociative polymers or large multi-subunit structures due to assembly failures. The instability of the dimer in aqueous solvents or inappropriate intradimer distances could cause major assembly failures. Polar solvation energies played a vital role too in forming assemble-incompetent dimers. Importantly, our study demonstrated that MD simulations on dimers can provide preliminary predictions on the assembly properties of HBc derivatives, thus aiding vaccine design by lowering the risk of self-assembling failures in engineered proteins.Communicated by Ramaswamy H. Sarma.

Mechanistic insights into the enzymatic activity of E3 ligase HOIL-1L and its regulation by the linear ubiquitin chain binding.

Heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1L) serves as a unique E3 ligase to catalyze the mono-ubiquitination of relevant protein or sugar substrates and plays vital roles in numerous cellular processes in mammals. However, the molecular mechanism underpinning the E3 activity of HOIL-1L and the related regulatory mechanism remain elusive. Here, we report the crystal structure of the catalytic core region of HOIL-1L and unveil the key catalytic triad residues of HOIL-1L. Moreover, we discover that HOIL-1L contains two distinct linear di-ubiquitin binding sites that can synergistically bind to linear tetra-ubiquitin, and the binding of HOIL-1L with linear tetra-ubiquitin can promote its E3 activity. The determined HOIL-1L/linear tetra-ubiquitin complex structure not only elucidates the detailed binding mechanism of HOIL-1L with linear tetra-ubiquitin but also uncovers a unique allosteric ubiquitin-binding site for the activation of HOIL-1L. In all, our findings provide mechanistic insights into the E3 activity of HOIL-1L and its regulation by the linear ubiquitin chain binding.

Proteomic Identification and Characterization of Collagen from Bactrian Camel (Camelus bactrianus) Hoof.

With the development of camel-derived food and pharmaceutical cosmetics, camel hoof, as a unique by-product of the camel industry, has gradually attracted the attention of scientific researchers in the fields of nutrition, health care, and biomaterial development. In this study, the protein composition and collagen type of Bactrian camel hoof collagen extract (CHC) were analyzed by LC-MS/MS, and the functional properties of CHC were further investigated, including its rheological characteristics, emulsification and emulsion stability, and hygroscopicity and humectancy. Proteomic identification confirmed that CHC had 13 collagen subunits, dominated by type I collagen (α1, α2), with molecular weights mainly in the 100-200 KDa range and a pI of 7.48. An amino acid study of CHC revealed that it carried the standard amino acid profile of type I collagen and was abundant in Gly, Pro, Glu, Ala, and Arg. Additionally, studies using circular dichroism spectroscopy and Fourier transform infrared spectroscopy revealed that CHC contains a collagen-like triple helix structure that is stable and intact. Different concentrations of CHC solutions showed shear-thinning flow behavior. Its tan δ did not differ much with increasing concentration. The CHC has good emulsifying ability and stability, humectancy, and hygroscopicity. This study provides a basis for utilizing and developing Bactrian camel hoof collagen as a functional ingredient.

Mechanistic Insights into the Interactions of Arl8b with the RUN Domains of PLEKHM1 and SKIP.

Arl8b, a specific Arf-like family GTPase present on lysosome, and plays critical roles in many lysosome-related cellular processes such as autophagy. The active Arl8b can be specifically recognized by the RUN domains of two Arl8b-effectors PLEKHM1 and SKIP, thereby regulating the autophagosome/lysosome membrane fusion and the intracellular lysosome positioning, respectively. However, the mechanistic bases underlying the interactions of Arl8b with the RUN domains of PLEKHM1 and SKIP remain elusive. Here, we report the two high-resolution crystal structures of the active Arl8b in complex with the RUN domains of PLEKHM1 and SKIP. In addition to elucidating the detailed molecular mechanism governing the specific interactions of the active Arl8b with the RUN domains of PLEKHM1 and SKIP, the determined complex structures also reveal a general binding mode shared by the PLEKHM1 and SKIP RUN domains for interacting with the active Arl8b. Furthermore, we uncovered a competitive relationship between the RUN domains of PLEKHM1 and SKIP in binding to the active Arl8b as well as a unique small GTPase-binding mode adopted by the PLEKHM1 and SKIP RUN domains, thereby enriching the repertoire of the RUN domain/small GTPase interaction modes. In all, our findings provide new mechanistic insights into the interactions of the active Arl8b with PLEKHM1 and SKIP, and are valuable for further understanding the working modes of these proteins in relevant cellular processes.

Self-powered PtNi-polyaniline films for converting rain energy into electricity.

Developing novel rainwater energy harvesting beyond conventional electricity is a promising strategy to address the problems of the energy crisis and environmental pollution. In this current work, a class of self-powered PtNi and optimal PtNi-polyaniline (PANI) films are successfully developed to convert rainwater into electricity for power generation. The maximized current, voltage and power of the self-powered PtNi-PANI films are 4.95 µA per droplet, 69.85 µV per droplet and 416.54 pW per droplet, respectively, which are attributed to the charging/discharging electrical signals between the cations provided by the rainwater and the electrons offered by the films. These results indicate that the optimized signal values are highly dependent on the elevated electron concentration of films, as well as the concentration, radius and charge of ions in rainwater. This work provides fresh insights into rain energy and enriches our knowledge of how to convert renewable energy into electricity generation.

Effect of Sodium Tanshinoneâ ¡A Sulfonate on Uric Acid, Sicam-1, ET-1 and FMD in Patients with Coronary Heart Disease Complicated with Hyperuricemia.

This study was to observe the effect of Sodium TanshinoneⅡA Sulfonate (ST-ⅡAS) on blood uric acid (UA), human Soluble Intercellular Adhesion Molecule-1 (sICAM-1), Endothelin-1 (ET-1) and percentage of brachial artery Flow-Mediated Dilatation (FMD) in individuals with Hyperuricemia Complicated Coronary Heart Disease (HC-CHD). The study's participants were 108 patients with HC-CHD who attended our hospital between January 2020 and June 2022. In the trial, the patients were split into two groups with 54 instances each: the general group and the observation group. The observation group received ST-IIAS therapy, while the general group received standard care. The experiment chose to observe and compare the difference of uric acid, sICAM-1, ET-1, FMD, therapeutic effectiveness and negative effects between the two groups at various times. Results showed that on the 14th day, the observation group's amounts of UA, sICAM-1, and ET-1 were inferior to the general group (P<0.05); On the 7th and 14th days, the observation group's amount of ET-1 was lower than that of the general group (P<0.05); The observation group's FMD of patients on the 14th day was inferior to the general group after treatment (P<0.05); The observation group's overall effective rate was 94.44% higher than the general group's (P<0.05); The observation group experienced fewer negative responses than the general group did (P<0.05). In conclusion, ST-ⅡAS can be used for uric acid, vascular endothelial systolic and diastolic function in patients with HC-CHD, and has better clinical efficacy and lower risk of adverse reactions.