Altered biliary microbial and metabolic profile reveals the crosstalk between NAFLD and cholelithiasis.

BACKGROUND: The relationship between non-alcoholic fatty liver disease (NAFLD) and cholelithiasis is intricate, with alterations in the microenvironment potentially mediating this interplay. Thus, this study aimed to explore the biliary microbiota and metabolites of patients with cholelithiasis and detect changes induced by comorbid NAFLD. METHODS: In this study, 16S rRNA gene sequencing and metabolome analysis were performed on biliary samples collected from 35 subjects. Then, patients were stratified into two groups: the comorbidity group (n=18), consisting of cholelithiasis patients with NAFLD, and the non-comorbidity group (n=17), comprising cholelithiasis patients without NAFLD. RESULTS: Comorbid NAFLD did not significantly increase α-diversity but affected ß-diversity. A statistically significant difference was observed in the abundance of biliary metabolites between the two groups. Specifically, differences in the abundance of 4 phyla, 19 genera, and 28 metabolites were significant between the two groups. Correlation analysis demonstrated positive associations among 12α-hydroxylated bile acid levels, Pyramidobacter and Fusobacterium abundance, AST levels, and the fibrosis-4 index (p < 0.05, r > 0.3), all of which were increased in patients with cholelithiasis and comorbid NAFLD. CONCLUSIONS: The relationship between cholelithiasis and NAFLD influences the biliary microbial and metabolic profile, creating a detrimental microenvironment that promotes the disease progression.

Time series analysis of the interaction between ambient temperature and air pollution on hospitalizations for AECOPD in Ganzhou, China.

This study aimed to investigate the univariate and bivariate effects of ambient temperature and air pollutants on 57,251 inpatients with AECOPD (Acute Exacerbation of Chronic Obstructive Pulmonary Disease) in Ganzhou from January 1, 2016, to December 31, 2019. We categorized the daily mean temperature and air pollutant variables based on the exposure-response curve of the Distributed Lag Non-Linear Model. Poisson regression model was used for interaction and stratification analysis. The Relative Excess Risk due to Interaction (RERI) with 95% confidence intervals (95% CI) between daily mean temperature (Tmean) and air pollutants including NO2, PM2.5, and PM10 were - 0.428 (95% CI - 0.637, - 0.218), -- 0.227 (95% CI - 0.293, - 0.161), and - 0.119 (95% CI - 0.159, - 0.079). Further stratification analysis showed the relative risk (RR) (95% CI) of high NO2 (> 33 µg/m3) at low Tmean (≤ 28 °C) was 1.119 (95% CI 1.096, 1.142). Low temperatures with high PM10 in men and high PM2.5 in women were associated with a higher risk of AECOPD hospitalization. The results indicate a higher risk of hospitalization for AECOPD when there is with high concentrations of air pollution at low temperatures.

Tannic acid coating gauze immobilized with thrombin with ultra-high coagulation activity and antimicrobial property for uncontrollable hemorrhage.

Rapid and safe hemostasis is crucial for the survival of bleeding patients in prehospital care. It is urgent to develop high performance hemostatic material to control the massive hemorrhage in the military field and accidental trauma. In this work, an efficient protein hemostat of thrombin was immobilized onto commercial gauze, which was mediated by self-polymerization and anchoring of tannic acid (TA). Through TA treatment, the efficient immobilization of thrombin was achieved, preserving both the biological activity of thrombin and the physical properties of the dressing, including absorbency, breathability, and mechanical performance. Moreover, in the presence of TA coating and thrombin, Gau@TA/Thr could obviously shortened clotting time and enriched blood components such as plasma proteins, platelets, and red blood cells, thereby exhibiting an enhanced in vitro coagulation effect. In SD rat liver volume defect and artery transection hemorrhage models, Gau@TA/Thr still had outstanding hemostatic performance. Besides, the Gau@TA/Thr gauze had inherent antibacterial property and demonstrated excellent biocompatibility. All results suggested that Gau@TA/Thr would be a potential candidate for treating uncontrollable hemorrhage in prehospital care.

Utilizing X-ray diffraction in conjunction with competitive adaptive reweighted sampling (CARS) and principal component analysis for the discrimination of medicinal pearl powder and nacre powder.

Nacre powder, often utilized to counterfeit medicinal pearl powder due to their similar chemical composition and appearance, poses a challenge in product authentication. This study introduces a rapid and efficient method for distinguishing between medicinal pearl powder and nacre powder using X-ray diffraction in conjunction with principal component analysis (PCA). The X-ray diffraction pattern underwent preprocessing techniques including smoothing denoising (Savitzky-Golay filter, 5-point) and second-order derivative analysis. Subsequently, PCA was employed for dimensionality reduction modeling. The CARS method was applied to select optimal variables for model refinement, determining the data preprocessing approach and key modeling variables. This method demonstrates the capability to accurately differentiate between pearl powder, nacre powder, and even counterfeit samples containing up to 90% pearl powder. With a high accuracy rate, swift operational speed, and potential for automation, this approach shows promise for practical implementation in the realm of pearl powder quality control.

Effects of ambient temperature and humidity on COPD mortality in Ganzhou city, China.

This study used the time series data of Ganzhou city to explore the individual and interaction effects of temperature and humidity on COPD death, and identify vulnerable subgroups of the population. We collected daily COPD mortality and meteorological data in Ganzhou from 2016 to 2019. The nonlinear distribution lag model was used to examine the associations and interaction between daily mean temperature and humidity and COPD mortality. For the total population, male and 65 years old or above, the relative risk (RR) for COPD mortality could be significant at extremely low temperature (3.3 ℃), reaching 1.799 (95% confidence interval [CI]: 1.216, 2.662), 1.894 (95% CI: 1.164, 3.084) and 1.779 (95% CI:1.185, 2.670). Also, at extremely low humidity (47.8%), the risk reached 1.888 (95% CI: 1.217, 2.930), 1.837 (95% CI: 1.066, 3.165) and 2.166 (95% CI: 1.375, 3.414). The cumulative COPD death risk for females was 3.524 (95% CI: 1.340, 9.267) at high temperature (30.7 ℃), 1.953(95% CI: 1.036, 3.683) at low humidity (47.8%) and 1.726 (95% CI: 1.048, 2.845) at high humidity (96.7%). For the total COPD deaths and subgroups, the interaction effects between daily temperature and humidity were not significant (p > 0.05). Both extremely low temperature and low humidity increased the risk of COPD death in Ganzhou city, especially for males and people over 65 years old. Females were more sensitive to extremely high temperature and humidity. Patients with COPD should pay attention to self-protection under extreme temperature and humidity weather conditions.

Cost-utility analysis and drug pricing for tirzepatide for type 2 diabetes in the Chinese market compared with semaglutide.

AIM: To investigate the most matchable price of tirzepatide (TIRZ) compared with semaglutide (SEMA) in the treatment of type 2 diabetes in China. METHODS: The patient cohort and clinical efficacy data were derived from the SURPASS-2 trial. Cost-utility analysis and a binary search were performed to identify the most matchable price of TIRZ from a Chinese healthcare provider's perspective. RESULTS: After lifetime simulation, the quality-adjusted life years of TIRZ 5, 10, 15 mg and SEMA 1 mg were 11.17, 11.21, 11.27 and 11.12 years, respectively. Despite an initial assumption that the annual cost of TIRZ equals that of SEMA, our analysis revealed that TIRZ is probably more cost-effective than SEMA. A thorough evaluation of pricing showed that the cost ranges for TIRZ at doses of 5, 10 and 15 mg were $1628.61-$1846.23, $1738.40-$2140.95 and $1800.30-$2430.81, respectively. After adjustment in the univariate sensitivity analysis, the cost ranges for TIRZ 5, 10 and 15 mg were $1542.68-$1757.57, $1573.00-$1967.16 and $1576.54-$2133.96, respectively. These cost intervals were validated through robust probabilistic sensitivity analysis and scenario analysis, except for the cost range for TIRZ 5 mg. CONCLUSIONS: This study shows that, using SEMA as a reference, the annual costs for TIRZ 10 and 15 mg are $1573.00-$1967.16 and $1576.54-$2133.96, respectively, for patients with type 2 diabetes in China.

Suppressed Phase Segregation with Small A-Site and Large X-Site Incorporation for Photostable Wide-Bandgap Perovskite Solar Cells.

Wide-bandgap (WBG) perovskite solar cells (PSCs) have been widely used as the top cell of tandem solar cells. However, photoinduced phase segregation and high open-circuit voltage loss pose significant obstacles to the development of WBG PSCs. Here, a two-step small-size A-site and large-size X-site incorporation strategy is reported to modulate the lattice distortion and improve the film quality of WBG formamidinium-methylammonium (FAMA) perovskite films for photostable PSCs based on two-step deposition method. First, CsI with content of 0-20% is introduced to tune the lattice distortion and film quality of FAMA perovskite with a bandgap of 1.70 eV. Then, 4% RbI is incorporated to further modulate the perovskite growth and lattice distortion, leading to the suppression of photoinduced phase segregation in the resultant RbCsFAMA quadruple cation perovskites. As a result, the 20%CsI/4%RbI-doped device obtains a promising efficiency of 20.6%, and the corresponding perovskite film shows good photothermal stability. Even without encapsulation, the device can maintain 92% of its initial efficiency after 1000 h of continuous operation under 1 sun equivalent white light-emitting diode illumination.

Thermodynamic Analysis of Silk Fibroin-Graphite Hybrid Materials and Their Morphology.

Silk fibroin (SF) is a ß-sheet-rich protein that is responsible for the remarkable tensile strength of silk. In addition to its mechanical properties, SF is biocompatible and biodegradable, making it an attractive candidate for use in biotic/abiotic hybrid materials. A pairing of particular interest is the use of SF with graphene-based nanomaterials (GBNs). The properties of this interface drive the formation of well-ordered nanostructures and can improve the electronic properties of the resulting hybrid. It was previously demonstrated that SF can form lamellar nanostructures in the presence of graphite; however, the equilibrium morphology and associated driving interactions are not fully understood. In this study, we characterize these interactions between SF and SF lamellar with graphite using molecular dynamics (MD) simulations and umbrella sampling (US). We find that SF lamellar nanostructures have strong orientational and spatial preferences on graphite that are driven by the hydrophobic effect, destabilizing solvent-protein interactions and stabilizing protein-protein and protein-graphite interactions. Finally, we show how careful consideration of these underlying interactions can be applied to rationally modify the nanostructure morphology.

Biomimetic Mineral Synthesis by Nanopatterned Supramolecular-Block Copolymer Templates.

Supramolecular structures of matrix proteins in mineralizing tissues are known to direct the crystallization of inorganic materials. Here we demonstrate how such structures can be synthetically directed into predetermined patterns for which functionality is maintained. The study employs block copolymer lamellar patterns with alternating hydrophilic and hydrophobic regions to direct the assembly of amelogenin-derived peptide nanoribbons that template calcium phosphate nucleation by creating a low-energy interface. Results show that the patterned nanoribbons retain their ß-sheet structure and function and direct the formation of filamentous and plate-shaped calcium phosphate with high fidelity, where the phase, amorphous or crystalline, depends on the choice of mineral precursor and the fidelity depends on peptide sequence. The common ability of supramolecular systems to assemble on surfaces with appropriate chemistry combined with the tendency of many templates to mineralize multiple inorganic materials implies this approach defines a general platform for bottom-up-patterning of hybrid organic-inorganic materials.

In Situ Polymerized Flame Retardant Gel Electrolyte for High-Performance and Safety-Enhanced Lithium Metal Batteries.

A flame retardant gel electrolyte (FRGE) is deemed as one of the most promising electrolytes to relieve the problems of safety hazards and interfacial incompatibility of Li metal batteries. Herein, a novel solvent triethyl 2-fluoro-2-phosphonoacetate (TFPA) with outstanding flame retardancy is introduced in the polymer skeleton synthesized by in situ polymerization of the monomer polyethylene glycol dimethacrylate (PEGDMA) and the cross-linker pentaerythritol tetraacrylate (PETEA). The FRGE exhibits superb interfacial compatibility with Li metal anodes and inhibits uncontrolled Li dendrite growth. This can be ascribed to the restriction of free phosphate molecules by the polymer skeleton, thus realizing a stable cycling performance over 500 h at 1 mA cm-2 and 1 mAh cm-2 in the Li||Li symmetric cell. In addition, the high ionic conductivity (3.15 mS cm-1) and Li+ transference number (0.47) of the FRGE further enhance the electrochemical performance of the correspondent battery. As a result, the LiFePO4|FRGE|Li cell exhibits excellent long-term cycling life with a capacity retention of 94.6% after 700 cycles. This work points to a new pathway for the practical development of high-safety and high-energy-density Li metal-based batteries.

Potential impacts of climate change on the distribution of the relict plant Shaniodendron subaequale.

Shaniodendron subeaqualis is a tertiary relict plant unique to China. This species has high greening, ecological, and scientific research value, and has been listed as a national I-level key protected plant. Clarifying the main climatic factors restricting the geographical distribution of S. subeaqualis and predicting the potential geographical distribution pattern of this species can provide a scientific basis for the protection of the germplasm resources of this rare species. Based on 104 S. subeaqualis natural distribution records and 9 climate factors, the MaxEnt software was used to predict the potential suitable areas of S. subeaqualis in different periods (LGM, MH, Current, SSP245-2050s, SSP245-2090s, SSP585-2050s, SSP585-2090s). The results showed that the contemporary AUC predicted by MaxEnt is 0.996, with high simulation accuracy; Precipitation in the driest season (Bio17), the average temperature in the coldest season (Bio11) are main factors affecting the distribution of S. subeaqualis. At present, the suitable area of S. subeaqualis is mainly distributed in Jiangsu, Anhui, and Zhejiang province, with a total area of 11.575 × 104 km2, of which the high suitable area is 1.424 × 104 km2 and the medium suitable area is 3.826 × 104 km2. In the LGM, the area of S. subeaqualis was roughly similar to that of the contemporary period, but there was a southward migration phenomenon in some areas, such as the suitable area in the south of Zhejiang. In order to avoid the influence of ice age, S. subeaqualis moved to nearby refuge places, such as Dabie Mountain area of Anhui province, the west of Tianmu Mountain area of Zhejiang province and mountain area of Jiangsu province. In the MH, the suitable area for S. subeaqualis was reduced and moved northward to a small extent. In the future period, the suitable range of S. subeaqualis will not change greatly, but the overall degree of fragmentation will intensify. If effective measures are not taken, it is bound to bring severe challenges to the survival of S. subeaqualis. In order to protect S. subeaqualis germplasm resources more effectively, it is suggested to dynamically monitor the existing S. subeaqualis population and take various measures actively to reduce the negative effects of climate change on S. subeaqualis.

Bidirectional association between NAFLD and gallstone disease: a systematic review and meta-analysis of observational studies.

BACKGROUND: Growing evidence indicates an association between NAFLD and gallstone disease (GD), while some does not support this. The aim of this meta-analysis was to evaluate the bidirectional association between NAFLD and GD. RESEARCH DESIGN AND METHODS: Five electronic databases were searched from inception to May 2022. The association was analyzed based on the odds ratio (OR) and 95% confidence interval (CI) with Reviewer Manager 5.3. RESULTS: Ten studies involving 284,512 participants met the criteria for GD predicting the onset of NAFLD. GD patients had a higher incidence of NAFLD (OR:1.48, CI:1.32-1.65, p < 0.00001), especially the incidence of moderate-to-severe NAFLD (OR:1.63; CI:1.40-1.79), with females at a higher risk (OR: 1.84; CI: 1.48-2.29). The inverse association was explored in eight studies involving 326,922 participants. The GD incidence in NAFLD patients was higher (OR:1.71, CI:1.63-1.79, p < 0.00001) and may increase due to female sex (OR: 4.18; CI: 1.21-14.37) and high BMI (OR: 1.80; CI: 1.36-2.56), compared with the non-NAFLD group. Besides, this bidirectional association was also confirmed in the Chinese population. CONCLUSIONS: The findings supported positive concurrent and bidirectional relationships between NAFLD and GD. Therefore, clinicians may alert the possibility of NAFLD in patients with GD and vice versa.

Cost-utility analysis of semaglutide for type 2 diabetes after its addition to the National Medical Insurance System in China.

INTRODUCTION: The main research purpose is to compare the long-term cost-effectiveness of semaglutide (SEMA) with that of dulaglutide (DULA) for patients with inadequately controlled type 2 diabetes throughout their lifetime. If necessary, the second aim is to investigate a further price cut for SEMA to provide sound advice for government drug price adjustments. METHODS: Cost-utility analysis was performed by the United Kingdom Prospective Diabetes Study Outcomes Model 2 (UKPDS OM2) from the perspective of health care providers in China. Baseline characteristics and clinical efficacy of SEMA and DULA were sourced from the high-dose comparison in the SUSTAIN-7 trial. A binary search was used to identify the scope for further reduction in the price of SEMA. The impact of individual parameters was assessed with sensitivity analyses. RESULTS: Main analysis (SEMA vs. DULA) revealed a mean difference in quality-adjusted life years (QALYs) of 0.04 QALYs and costs of $1132.29. The incremental cost-utility ratio was $26 957.44/QALY, showing that SEMA was a better option compared with DULA. In sensitivity analyses, the discount rate made the greatest contribution to the incremental cost-utility ratio. In the binary search, there was still scope to reduce the SEMA cost further by approximately 6.83% to be cost-effective, taking DULA as a reference. CONCLUSION: After its addition to the National Medical Insurance System in China, SEMA is expected to be a cost-effective choice compared with DULA for patients with type 2 diabetes with inadequately controlled from the cost-utility analysis. However, there is still scope to reduce the annual cost of SEMA further.

Association between daily temperature and hospital admissions for urolithiasis in Ganzhou, China: a time-series analysis.

Urolithiasis was a global disease and it was more common in southern China. This study looked into the association between daily temperature and urolithiasis hospital admissions in Ganzhou, a large prefecture-level city in southern China. In Ganzhou City from 2016 to 2019, a total of 60,881 hospitalized cases for urolithiasis from 69 hospitals and meteorological data were gathered. The effect of high ambient temperature on urolithiasis hospital admissions was estimated using a distributed lag nonlinear model. Stratified analysis was done to examine sex differences. The study found that in Ganzhou of China, the exposure-response curves approximated a "J" shape which across genders were basically similar. The maximum lag effect occurred on the second day after high temperatures for males but on the third day for females. Compared to the 10 °C reference temperature and considering the cumulative lag effect of 10 days, the relative risks of the daily mean temperature at the 95th percentile on the total, male, and female hospital admissions for urolithiasis were 2.026 (95% CI: 1.628, 2.521), 2.041 (95% CI: 1.603, 2.598), and 2.030 (95% CI: 1.552, 2.655), respectively, but the relative risks between sex were not statistically significant (p = 0.977). Urolithiasis morbidity risk in China could be exacerbated by high temperatures. The effect of high temperature on urolithiasis was similar across genders.

Capture and detection of Escherichia coli with graphene aerogels.

Some pathogenic bacteria may cause serious food poisoning as well as catastrophic infections. Thus, it is critical to identify bacteria using simple, quick, and sensitive methods. Herein, we fabricate a graphene aerogel-based biosensing system to capture and detect Escherichia coli (E. coli) with high specificity and sensitivity. A graphene aerogel is prepared by a one-step hydrothermal synthesis method without any reducing reagent. With the help of E. coli antibodies and the graphene foam with a porous structure, E. coli can be captured using the detection substrate with high specificity and selectivity. The electrical resistance and electrochemical impedance spectroscopy (EIS) results of the graphene aerogel foam changed with high sensitivity during E. coli adhesion. Moreover, the resistance change of the graphene device can still be observed when the E. coli concentration was as low as 10 cfu mL-1, while there is no obvious resistance change in the use of Staphylococcus aureus. The subsequent EIS test also found that the charge transfer resistance (Rct) of the detection substrate gradually increased during the E. coli capture process. This nanoelectronic biosensor is simple, quick, safe, and very sensitive, and it may be used as a high-throughput platform for pathogenic bacterial detection, bacterial research, and antimicrobial drug screening.

Luminescence-enhanced conjugated polymer dots through thermal treatment for cell imaging.

Conjugated polymer dots (Pdots) are often used as excellent fluorescent probes in the biomedical field. In the process of preparing Pdots, the rapid change of the solvent polarity will result in a messy and defective stacking of the polymer chains in the particle, and these stacking defects of the polymer chains may weaken its luminescence properties. Here, we try to optimize the stacking of the conjugated polymer chains by the thermal annealing treatment. After the low temperature thermal treatment, the fluorescence intensity of Pdots can be enhanced by about 11%-29%, and Pdots maintain their original stability and biosafety. We used transmission electron microscopy (TEM) and single particle fluorescence imaging to reveal the possible mechanism of the chain stacking optimization process, that is, the thermal annealing process of Pdots is the competition between internal chain rearrangement in the particle and particle aggregation. The luminescence-enhanced Pdots exhibit good cellular imaging performance. These results prove that it is feasible to extend the thermal annealing treatment from planar polymer devices to polymer nanoparticles. It provides the possibility to realize stable and complex biological imaging applications using Pdots with a simple molecular structure, and a mature improvement scheme for the mass preparation of Pdots.

Anisotropic Molecular Organization at a Liquid/Vapor Interface Promotes Crystal Nucleation with Polymorph Selection.

The molecules at the surface of a liquid have different organization and dynamics from those in the bulk, potentially altering the rate of crystal nucleation and polymorphic selection, but this effect remains poorly understood. Here we demonstrate that nucleation at the surface of a pure liquid, d-arabitol, is vastly enhanced, by 12 orders of magnitude, and selects a different polymorph. The surface effect intensifies with cooling and can be inhibited by a dilute, surface-active second component. This phenomenon arises from the anisotropic molecular packing at the interface and its similarity to the surface-nucleating polymorph. Our finding is relevant for controlling the crystallization and polymorphism in any system with a significant interface such as nanodroplets and atmospheric water.

Robust Prediction of Prognosis and Immunotherapy Response for Bladder Cancer through Machine Learning Algorithm.

The important roles of machine learning and ferroptosis in bladder cancer (BCa) are still poorly understood. In this study, a comprehensive analysis of 19 ferroptosis-related genes (FRGs) was performed in 1322 patients with BCa from four independent patient cohorts and a pan-cancer cohort of 9824 patients. Twelve FRGs were selected through machine learning algorithm to construct the prognosis model. Significantly differential survival outcomes (hazard ratio (HR) = 2.09, 95% confidence interval (CI): 1.55−2.82, p < 0.0001) were observed between patients with high and low ferroptosis scores in the TCGA cohort, which was also verified in the E-MTAB-4321 cohort (HR = 4.71, 95% CI: 1.58−14.03, p < 0.0001), the GSE31684 cohort (HR = 1.76, 95% CI: 1.08−2.87, p = 0.02), and the pan-cancer cohort (HR = 1.15, 95% CI: 1.07−1.24, p < 0.0001). Tumor immunity-related pathways, including the IL-17 signaling pathway and JAK-STAT signaling pathway, were found to be associated with the ferroptosis score in BCa through a functional enrichment analysis. Further verification in the IMvigor210 cohort revealed the BCa patients with high ferroptosis scores tended to have worse survival outcome after receiving tumor immunotherapy. Significantly different ferroptosis scores could also be found between BCa patients with different reactions to treatment with immune checkpoint inhibitors.

Blocking CD47 Shows Superior Anti-tumor Therapeutic Effects of Bevacizumab in Gastric Cancer.

Background: Bevacizumab (Avastin®), a humanized antiangiogenic monoclonal antibody, is widely used in the clinical treatment of tumour diseases. However, recent research has shown that the beneficial antiangiogenic effects of these agents have been limited in a number of patients due to complex immunosuppressive mechanisms. Here, we report a synergistic antitumour strategy through simultaneous blockade of VEGF and CD47 signalling to enhance the curative effect of advanced gastric cancer. Method: A BGC-823 gastric tumour model was chosen to evaluate antitumour efficacy. Macrophage migration and phagocytosis were evaluated to determine immune-related resistance to bevacizumab therapy. Synergistic antitumour activity was observed on the basis of tumour volume, tumour weight, tumour inhibition rate, tumour angiogenesis and tumour metastasis when bevacizumab was combined with an anti-CD47 monoclonal antibody. Results: Our study demonstrated that synergistic therapy targeting CD47 and VEGF reversed macrophage migration and phagocytosis, which were inhibited by antiangiogenic therapy and enhanced antitumour effects. Moreover, blockade of CD47 induced by antiangiogenic therapy inhibited tumour metastasis. Conclusion: Our data provide an effective strategy to attenuate resistance to bevacizumab therapy, promoting clinical cancer treatment with antiangiogenic drugs in combination with CD47-targeting inhibitors.