First-line hepatic arterial infusion chemotherapy plus lenvatinib and PD-(L)1 inhibitors versus systemic chemotherapy alone or with PD-(L)1 inhibitors in unresectable intrahepatic cholangiocarcinoma.

PURPOSE: Limited treatment options exist for unresectable intrahepatic cholangiocarcinoma (ICC), with systemic chemotherapy (SC) serving as the primary approach. This study aimed to assess the effectiveness of first-line hepatic arterial infusion chemotherapy (HAIC) in combination with lenvatinib and PD-(L)1 inhibitors (HLP) compared to SC combined with PD-(L)1 inhibitors (SCP) or SC alone in treating unresectable ICC. METHODS: Patient with unresectable ICC who underwent first-line treatment with HLP, SCP or SC from January 2016 to December 2022 were retrospectively analyzed. The study evaluated and compared efficacy and safety outcomes across the three treatment groups. RESULTS: The study comprised 42, 49, and 50 patients in the HLP, SCP, and SC groups, respectively. Median progression-free survival (PFS) times were 30.0, 10.2, and 6.5 months for HLP, SCP, and SC groups. While the SC group had a median overall survival (OS) time of 21.8 months, the HLP and SCP groups hadn't reached median OS. The HLP group demonstrated significantly superior PFS (p < 0.001) and OS (p = 0.014) compared to the others. Moreover, the HLP group exhibited the highest objective response rate (ORR) at 50.0% and the highest disease control rate (DCR) at 88.1%, surpassing the SC group (ORR, 6.0%; DCR, 52.0%) and SCP group (ORR, 18.4%; DCR, 73.5%) (p < 0.05). Generally, the HLP group reported fewer grades 3-4 adverse events (AEs) compared with others. CONCLUSION: In contrast to systemic chemotherapy with or without PD-(L)1 inhibitors, the triple combination therapy incorporating HAIC, lenvatinib, and PD-(L)1 inhibitors showcased favorable survival benefits and manageable adverse events for unresectable ICC.

S-scheme heterojunction phthalocyanine/TiO2 photoelectrochemical sensor for innovative glutathione detection.

A novel photoelectrochemical sensor, employing an S-scheme heterojunction of phthalocyanine and TiO2 nanoparticles, has been developed to enable highly sensitive determination of glutathione. By integrating the favorable stability, environmental benignity, and electronic properties of the TiO2 matrix with the unique photoactivity of phthalocyanine species, the designed sensor presents a substantial linear dynamic range and a low detection limit for the quantification of glutathione. The sensitivity is attributed to efficient charge transfer and separation across the staggered heterojunction energy levels, which generates measurable photocurrent signals. Systematic variation of phthalocyanine content reveals an optimal composition that balances light harvesting capacity and electron-hole recombination rates. The incorporation of phosphotungstic acid (PTA) in sample preparation effectively minimizes interference from compounds like L-cysteine and others. Consequently, this leads to an improvement in accuracy through the reduction of impurity levels. Appreciable photocurrent enhancements are observed upon introduction of both oxidized and reduced glutathione at the optimized composite photoanode. Coupled with advantageous features of photoelectrochemical transduction such as simplicity, cost-effectiveness, and resistance to fouling, this sensor holds great promise for practical applications in complex biological media.

A review of the extraction and purification methods, biological activities, and applications of active compounds in Acanthopanax senticosus.

Acanthopanax senticosus (AS) is a geo-authentic crude medicinal plant that grows in China, Korea, Russia, and Japan. AS contains bioactive compounds such as eleutherosides, polysaccharides, and flavonoids. It is also a key traditional herb in the Red List of Chinese Species. AS is mainly distributed in Northeast China, specifically in Heilongjiang, Jilin, and Liaoning provinces. Its active compounds contribute to significant biological activities, including neuroprotective, antioxidant, anti-fatigue, and antitumor effects. However, the extraction methods of active compounds are complex, the extraction efficiency is poor, and the structure-activity relationship is unclear. This study focused on the nutrients in AS, including protein, carbohydrates, and lipids. Particularly, the active ingredients (eleutherosides, polysaccharides, and flavonoids) in AS and their extraction and purification methods were analyzed and summarized. The biological activities of extracts have been reviewed, and the mechanisms of anti-oxidation, antitumor, anti-inflammation, and other activities are introduced in detail. The applications of AS in various domains, such as health foods, medicines, and animal dietary supplements, are then reported. Compared with other extraction methods, ultrasonic or microwave extraction improves efficiency, yet they can damage structures. Challenges arise in the recovery of solvents and in achieving extraction efficiency when using green solvents, such as deep eutectic solvents. Improvements can be made by combining extraction methods and controlling conditions (power, temperature, and time). Bioactive molecules and related activities are exposited clearly. The applications of AS have not been widely popularized, and the corresponding functions require further development.

Paeoniflorin regulates RhoA/ROCK1 and Nrf2 pathways in PDLIM1-dependent or independent manners in oxidative stressed melanocytes.

BACKGROUND: The adhesive properties of vitiligo melanocytes have decreased under oxidative stress., cytoskeleton proteins can control cell adhesion. Paeoniflorin (PF) was proved to resist hydrogen peroxide (H2O2)-induced oxidative stress in melanocytes via nuclear factorE2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. OBJECTIVES: This study was to investigate whether PF exerts anti-oxidative effect through influencing cytoskeleton markers or potential signaling pathway. METHODS: Human Oxidative Stress Plus array was used to identify the differentially expressed genes between H2O2 + PF group and H2O2 only group, in PIG1 and PIG3V melanocyte cell lines respectively. Western blotting was used to verify the PCR array results and to test the protein expression levels of cytoskeleton markers including Ras homolog family member A (RhoA), Rho-associated kinase 1 (ROCK1) and antioxidative marker Nrf2. Small interfering RNA was used to knock down PDZ and LIM domain 1 (PDLIM1). RESULTS: PF increased the expressions of PDLIM1, RhoA and ROCK1 in H2O2-induced PIG1, in contrast, decreased the expressions of PDLIM1 and ROCK1 in H2O2-induced PIG3V. Knockdown of PDLIM1 increased the expressions of RhoA and Nrf2 in PF-pretreated H2O2-induced PIG1, and ROCK1 and Nrf2 in PF-pretreated H2O2-induced PIG3V. CONCLUSIONS: PF regulates RhoA/ROCK1 and Nrf2 pathways in PDLIM1-dependent or independent manners in H2O2-induced melanocytes. In PIG1, PF promotes PDLIM1 to inhibit RhoA/ROCK1 pathway or activates Nrf2/HO-1 pathway, separately. In PIG3V, PF directly downregulates ROCK1 in PDLIM1-independent manner or upregulates Nrf2 dependent of PDLIM1.

Pressureless Welding of Temperature-Invariant Multifunctionality Body Based on Hydroxyl-Functionalized Boron Nitride Nanosheets and Bifunctional Monoethanolamine Cross-linker.

Bulk hexagonal boron nitride (h-BN) ceramics with structural integrity, high-temperature resistance and low expansion rate are expected for multifunctional applications in extreme conditions. However, due to its sluggish self-diffusion and intrinsic inertness, it remains a great challenge to overcome high-energy barrier for h-BN powder sintering. Herein, a cross-linking and pressureless-welding strategy is reported to produce bulk boron nitride nanosheets (BNNSs) ceramics with well-crystalized and dense B-N covalent-welding frameworks. The essence of this synthesis strategy lies in the construction of >B─O─H2C─H2C─H2N:→B< bond bridge connection structure among hydroxyl functionalized BNNSs (BNNSs-OH) using bifunctional monoethanolamine (MEA) as cross-linker through esterification and intermolecular-coordination reactions. The prepared BNNSs-interlaced ceramics have densities not less than 1.2 g cm-3, and exhibit exceptional mechanical robustness and resiliency, excellent thermomechanical stability, ultra-low linear thermal expansion coefficient of 0.06 ppm °C-1, and high thermal diffusion coefficient of 4.76 mm2 s-1 at 25 °C and 3.72 mm2 s-1 at 450 °C. This research not only reduces the free energy barrier from h-BN particles to bulk ceramics through facile multi-step physicochemical reaction, but also stimulates further exploration of multifunctional applications for bulk h-BN ceramics over a wide temperature range.

Temporal dynamics of Grime's CSR strategies in plant communities during 60 years of succession.

Grime's competitive, stress-tolerant, ruderal (CSR) theory predicts a shift in plant communities from ruderal to stress-tolerant strategies during secondary succession. However, this fundamental tenet lacks empirical validation using long-term continuous successional data. Utilizing a 60-year longitudinal data of old-field succession, we investigated the community-level dynamics of plant strategies over time. Our findings reveal that while plant communities generally transitioned from ruderal to stress-tolerant strategies during succession, initial abandonment conditions crucially shaped early successional strategies, leading to varied strategy trajectories across different fields. Furthermore, we found a notable divergence in the CSR strategies of alien and native species over succession. Initially, alien and native species exhibited similar ruderal strategies, but in later stages, alien species exhibited higher ruderal and lower stress tolerance compared to native species. Overall, our findings underscore the applicability of Grime's predictions regarding temporal shifts in CSR strategies depending on both initial community conditions and species origin.

Upregulated dual oxidase 1-induced oxidative stress and caspase-1-dependent pyroptosis reflect the etiologies of heart failure.

BACKGROUND: Oxidative stress is implicated in the pathogenesis of heart failure. Dual oxidase 1 (DUOX1) might be important in heart failure development through its mediating role in oxidative stress. This study was designed to evaluate the potential role of DUOX1 in heart failure. MATERIALS AND METHODS: AC16 cells were treated with 2 µmol/L of doxorubicin (DOX) for 12, 24, and 48 h to construct a heart failure model. DUOX1 overexpression and silencing in AC16 cell were established. DUOX1 expression was detected by Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Pyroptosis and reactive oxygen species (ROS) production were measured by flow cytometry. RESULTS: Increased DUOX1 expression levels were observed after DOX treatment for 24 h in AC16 cells. DUOX1 silencing inhibited DOX-induced pyroptosis and ROS production. The release of IL-1ß, IL-18, and lactate dehydrogenase (LDH), and expression levels of pyroptosis-related proteins were also decreased. DUOX1 overexpression increased pyroptosis, ROS production, IL-1ß, IL-18, and LDH release, and pyroptosis-related protein expression. N-acetyl-cysteine (NAC) significantly reversed DUOX1-induced pyroptosis, ROS, and related factors. CONCLUSION: These results suggest that DUOX1-derived genotoxicity could promote heart failure development. In the process, oxidative stress and pyroptosis may be involved in the regulation of DUOX1 in heart failure.

In silico genome-wide analysis of homeodomain-leucine zipper transcription factors in Cannabis sativa L.

HD-Zip (Homeodomain-Leucine Zipper) is a family of transcription factors unique to higher plants and plays a vital role in plant growth and development. Increasing research results show that HD-Zip transcription factors are widely involved in many life processes in plants. However, the HD-Zip transcription factor for cannabis, a valuable crop, has not yet been identified. The sequence characteristics, chromosome localization, system evolution, conservative motif, gene structure, and gene expression of the HD-Zip transcription factor in the cannabis genome were systematically studied. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to verify its function. The results showed that cannabis contained 33 HD-Zip gene members. The number of amino acids is 136-849aa, the isoelectric point is 4.54-9.04, and the molecular weight is 23264.32-93147.87Da. Many cis-acting elements are corresponding to hormone and abiotic stress in the HD-Zip family promoter area of cannabis. Sequencing of the transcriptome at 5 tissue sites of hemp, stems, leaves, bracts, and seeds showed similar levels of expression of 33 members of the HD-Zip gene family at 5 tissue sites. Bioinformatics results show that HD-Zip expression is tissue-specific and may be influenced by hormones and environmental factors. This lays a foundation for further research on the gene function of HD-Zip.

The association between systemic inflammatory response index and contrast-associated acute kidney injury in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: The systemic inflammatory response index (SIRI), served as a novel inflammatory biomarker, is the synthesis of neutrophils, monocytes and lymphocytes. AIMS: We hypothesized that SIRI has predictive value for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: We retrospectively observed 5685 patients undergoing elective PCI from January 2012 to December 2018. Venous blood samples were collected to obtain the experimental data on the day of admission or the morning of the next day. SIRI = neutrophil count × monocyte count/lymphocyte count. CA-AKI was defined as an increase of 50% or 0.3 mg/dl in SCr from baseline within 48 h after contrast exposure. RESULTS: The incidence of CA-AKI was 6.1% (n = 352). The best cutoff value of SIRI for predicting CA-AKI was 1.39, with a sensitivity of 52.3% and a specificity of 67.3%. [AUC: 0.620, 95% confidence interval (CI): 0.590-0.651, p < 0.001]. After adjusting for potential confounders, multivariate analysis showed that the high SIRI group (SIRI > 1.39) was a strong independent predictor of CA-AKI in patients undergoing elective PCI compared with the low SIRI group (SIRI ≤ 1.39) (odds ratio = 1.642, 95% CI: 1.274-2.116, p < 0.001). Additionally, COX regression analysis showed that SIRI > 1.39 was significantly associated with long-term mortality at a median follow-up of 2.8 years. [Hazard ratio (HR)=1.448, 95%CI: 1.188-1.765; p < 0.001]. Besides, Kaplan-Meier survival curve also indicated that the cumulative rate of mortality was considerably higher in the high SIRI group. CONCLUSIONS: High levels of SIRI are independent predictors of CA-AKI and long-term mortality in patients undergoing elective PCI.

Recent trends in extraction, purification, structural characterization, and biological activities evaluation of Perilla frutescens (L.) Britton polysaccharide.

Perilla frutescens (L.) Britton is an annual herb plant of the Perilla genus in the Labiatae family, which is commonly utilized as an edible and medicinal resource. Polysaccharides are among the major components and essential bioactive compounds of P. frutescens, which exhibit a multitude of biological activities, including antioxidant, antitumor, anti-fatigue, immunoregulation, hepatoprotective, anti-inflammatory, and lipid-lowering effects. As a natural carbohydrate, P. frutescens polysaccharide has the potential to be utilized in the development of drugs and functional materials. In this paper, we provide an overview of progress made on the extraction, purification, structural characterization, and bioactivity of polysaccharides from different parts of P. frutescens. The challenges and opportunities for research are discussed, along with the potential development prospects and future areas of focus in the study of P. frutescens polysaccharides.

Development of D-π-A organic dyes for discriminating HSA from BSA and study on dye-HSA interaction.

HSA (human serum albumin), a most abundant protein in blood serum, plays a key role in maintaining human health. Abnormal HSA level is correlated with many diseases, and thus has been used as an essential biomarker for therapeutic monitoring and biomedical diagnosis. Development of small-molecule fluorescent probes allowing the selective and sensitive recognition of HSA in in vitro and in vivo is of fundamental importance in basic biological research as well as medical diagnosis. Herein, we reported a series of new synthesized fluorescent dyes containing D-π-A constitution, which exhibited different optical properties in solution and solid state. Among them, dye M-H-SO3 with a hydrophilic sulfonate group at electron-acceptor part displayed selectivity for discrimination of HSA from BSA and other enzymes. Upon binding of dye M-H-SO3 with HSA, a significant fluorescence enhancement with a turn-on ratio about 96-fold was triggered. The detection limit was estimated to be âˆ¼ 40 nM. Studies on the interaction mechanism revealed that dye M-H-SO3 could bind to site III of HSA with a 1:1 binding stoichiometry. Furthermore, dye M-H-SO3 has been applied to determine HSA in real urine samples with good recoveries, which provided a useful method for HSA analysis in biological fluids.

Comparative analysis of surgical outcomes in children with type 3 and type 4 lateral physeal condylar humerus fractures in China: Closed Reduction-PerCutaneous Pinning (CRPP) vs. Open Reduction-Internal Fixation (ORIF).

Background: Lateral physeal condylar humerus fractures in pediatric patients aged 1-13 rank as the second most common elbow injury, occurring with a frequency ranging from 5% to 16.8%. There exists an ongoing debate regarding the surgical management of these fractures. This study aims to evaluate the efficacy of Open Reduction and Internal Fixation (ORIF) and Closed Reduction and Percutaneous Pinning (CRPP) as suitable surgical treatments for displaced unstable fractures of the lateral condyle physeal humerus in children. The comparison encompasses the results of ORIF and CRPP, alongside clinical and radiographic outcomes and complication rates. Method: A retrospective review was conducted at the Department of Orthopedic Surgery in the research hospital. A cohort of 27 patients treated between 2016 and 2023 were analyzed, 19 patients meeting inclusion criteria. The fracture pattern and degree of displacement were assessed, with specialized radiologists, doctors, and surgeons in agreement. Among the patients, 11 underwent CRPP 7 type 3and 4 type 2, while 16 received ORIF 12 type 4 and 4 type 5. Data collection included fracture type, surgical method, operation time, pre and post-operative displacement, casting period, bone union condition, follow-up records, range of motion, complications, delayed union, lateral spurring, and pin removal records. Results: For CRPP, the mean time for pin removal was 5.42 weeks, with excellent bone union and an average operation time of 34.57 min. Criteria of Hardacre showed 28.57% of cases as good and 71.42% as excellent. Similarly, ORIF demonstrated a mean operation time of 42.5 min, with the fracture healing within 5.33 weeks and the pin being removed after 15 days on average. Criteria of Hardacre indicated 25% of cases as good and 75% as excellent. Both groups showed satisfactory outcomes, with no complications such as osteomyelitis, nonunion, malunion, delayed union, myositis ossificans, physeal growth arrest, tardy ulnar nerve palsy, cubitus valgus, or varus, and no cases requiring re-surgery. Conclusion: Both CRPP and ORIF are effective surgical methods for treating lateral physeal condylar humeral fractures (types 3 and 4 according to the Song classification) in children, demonstrating satisfactory outcomes. Notably, regardless of displacement (2 mm and >2 mm), both methods yield similar results, albeit with CRPP offering the advantage of avoiding incisions. Overall, both procedures are safe, with favorable bone healing outcomes.

Synergistic acceleration of machine learning and molecular docking for prostate-specific antigen ligand design.

Prostate-specific antigen (PSA) serves as a critical biomarker for the early detection and continuous monitoring of prostate cancer. However, commercial PSA detection methods primarily rely on antigen-antibody interactions, leading to issues such as high costs, stringent storage requirements, and potential cross-reactivity due to PSA variant sequence homology. This study is dedicated to the precise design and synthesis of molecular entities tailored for binding with PSA. By employing a million-level virtual screening to obtain potential PSA compounds and effectively guiding the synthesis using machine learning methods, the resulting lead compounds exhibit significantly improved binding affinity compared to those developed before by researchers using high-throughput screening for PSA, substantially reducing screening and development costs. Unlike antibody detection, the design of these small molecules offers promising avenues for advancing prostate cancer diagnostics. Furthermore, this study establishes a systematic framework for the rapid development of customized ligands that precisely target specific protein entities.

Chromium immobilization from wastewater via iron-modified hydrochar: Different iron fabricants and practicality assessment.

The recycling of industrial solid by-products such as red mud (RM) has become an urgent priority, due to their large quantities and lack of reutilization methods can lead to resource wastage. In this work, RM was employed to fabricate green hydrochar (HC) to prepare zero-valent iron (ZVI) modified carbonous materials, and conventional iron salts (IS, FeCl3) was applied as comparison, fabricated HC labeled as RM/HC and IS/HC, respectively. The physicochemical properties of these HC were comprehensively characterized. Further, hexavalent chromium (Cr(VI)) removal performance was assessed (375.66 and 337.19 mg/g for RM/HC and IS/HC, respectively). The influence of dosage and initial pH were evaluated, while isotherms, kinetics, and thermodynamics analysis were also conducted, to mimic the surface interactions. The stability and recyclability of adsorbents also verified, while the practical feasibility was assessed by bok choy-planting experiment. This work revealed that RM can be used as a high value and green fabricant for HC the effective removal of chromium contaminants from the wastewater.

Complications and psychological impact of pressure ulcers on patients and caregivers.

Pressure ulcers are persistent skin lesions that have substantial detrimental effects on the physical well-being of patients. Moreover, their psychological ramifications for both patients and their caregivers are becoming more widely acknowledged. This research was conducted to examine the psychological ramifications of pressure ulcers and ascertain efficacious approaches to mitigate these effects and improve overall well-being. A cross-sectional study was conducted from March 2022 to December 2023 across tertiary care centres located in Beijing. The cohort consisted of 431 participants, which included primary caregivers and patients who were diagnosed with pressure ulcers. The data were gathered through the utilization of structured questionnaires and semi-structured interviews. These methods encompassed demographic details, clinical characteristics and validated scales that assessed psychological parameters, including quality of life, anxiety, stress and depression. The research exposed substantial psychological toll on both individuals receiving care and those providing care, with caregivers enduring diminished quality of life and elevated levels of anxiety, depression and stress (p < 0.05). A significant positive correlation was identified between the degree of psychological distress and severity of pressure ulcers (p < 0.05). Both location of the ulcer and duration of care were substantial contributors to the psychological burden (p < 0.05). In spite of the apparent necessity, a significant proportion of the participants refrained from obtaining psychological counselling. The results underscored the significant psychological ramifications of pressure ulcers for both individuals receiving care and the caregivers. As a result, comprehensive care strategies that incorporate psychological assistance into the prescribed treatment plan are imperative. This research highlighted the criticality of implementing all-encompassing, interdisciplinary approaches to tackle the complex issues presented by pressure ulcers in an effort to enhance the general welfare of those influences.

Effects of the Hydroxy-Regulated Li-Montmorillonite Atomic Interface Arrangement on Li Cycle of Marine Sedimentation and pH.

The reaction of ubiquitous clay is related to the global cycle of the key metals, but the relationship between the Li occurrence interface and the sedimentation in the Li cycle remains unclear. We investigated the atomic interface arrangement of Li-montmorillonite (Li-Mt) during low-temperature water-rock reactions and Li migration. The results show that, in Cl-rich systems, deprotonation and exposure of Na adsorption sites cause Li enrichment and O pairing, which lead to the weakening of the shielding effect of Mt on anions and the formation of a Mt-Li-Cl atomically interfacial arrangement. Only up to 20.3% of the Li is contained in the atomic interface of Li-Mt. In F-rich system, the dehydroxylation of F paired with Al in octahedral sites causes Li accumulation via local crystallization of LiF, and co-complexation of F and Li forms a Mt(Al)-F-Li atomic interface, in which up to 46.8% of the Li is enriched by the Mt. The participation of F and Cl in the complexation intensifies lattice collapse of the Li-Mt edge. The sedimentation velocity decreases with the smaller particle size affected by the Li loading. Lithium leached from igneous rocks serves as the marine Li source, which contributes up to 99.8% and 99.5% of the Li in Cl- and F-rich systems, respectively. The response of Mt(OH) to Li migration with a time accumulating effect may make an important regulatory of oceanic pH by either acidification or alkalization.

Unveiling complete natural reductive dechlorination mechanisms of chlorinated ethenes in groundwater: Insights from functional gene analysis.

Monitored natural attenuation (MNA) of chlorinated ethenes (CEs) has proven to be a cost-effective and environment-friendly approach for groundwater remediation. In this study, the complete dechlorination of CEs with formation of ethene under natural conditions, were observed at two CE-contaminated sites, including a pesticide manufacturing facility (PMF) and a fluorochemical plant (FCP), particularly in the deeply weathered bedrock aquifer at the FCP site. Additionally, a higher abundance of CE-degrading bacteria was identified with heightened dechlorination activities at the PMF site, compared to the FCP site. The reductive dehalogenase genes and Dhc 16 S rRNA gene were prevalent at both sites, even in groundwater where no CE dechlorination was observed. vcrA and bvcA was responsible for the complete dechlorination at the PMF and FCP site, respectively, indicating the distinct contributions of functional microbial species at each site. The correlation analyses suggested that Sediminibacterium has the potential to achieve the complete dechlorination at the FCP site. Moreover, the profiles of CE-degrading bacteria suggested that dechlorination occurred under Fe3+/sulfate-reducing and nitrate-reducing conditions at the PMF and FCP site, respectively. Overall these findings provided multi-lines of evidence on the diverse mechanisms of CE-dechlorination under natural conditions, which can provide valuable guidance for MNA strategies implementation.

The Association of Intraindividual Difference Between Cystatin- and Creatinine-Based Estimated GFR and Contrast-Associated Acute Kidney Injury.

Purpose: The estimated glomerular filtration rate (eGFR) based on creatinine is crucial for the risk assessment of contrast-associated acute kidney injury (CA-AKI). In recent, the difference between cystatin C-based eGFR (eGFRcys) and creatinine-based eGFR (eGFRcr) has been widely documented. We aimed to explore whether intraindividual differences between eGFRcys and eGFRcr had potential value for CA-AKI risk assessment in patients undergoing elective percutaneous coronary intervention (PCI). Patients and Methods: From January 2012 to December 2018, we retrospectively observed 5049 patients receiving elective PCI. To determine eGFR, serum creatinine and cystatin C levels were measured. CA-AKI was defined as serum creatinine being increased ≥ 50% or 0.3 mg/dL within 48 h after contrast agents exposure. Chronic kidney disease (CKD) was defined as the eGFR < 60 mL/min/1.73 m2. Results: Approximately half of the participants (2479, 49.1%) had a baseline eGFRdiff (eGFRcys-eGFRcr) between -15 and 15 mL/min/1.73 m2. Restricted cubic splines analysis revealed a nonlinear relationship between eGFRdiff and CA-AKI. Multivariable logistic regression analysis indicated that compared with the reference group (-15 to 15 mL/min/1.73 m2), the negative-eGFRdiff group (less than -15 mL/min/1.73 m2) had a higher risk of CA-AKI (OR, 3.44; 95% CI, 2.57-4.64). Furthermore, patients were divided into four groups based on CKD identified by eGFRcys or eGFRcr. Multivariable logistic analysis revealed that patients with either CKDcys (OR, 2.94; 95% CI, 2.19-3.95, P < 0.001) or CKDcr (OR, 2.44; 95% CI, 1.19-4.63, P < 0.001) had an elevated risk of CA-AKI compared to those without CKDcys and CKDcr. Conclusion: There are frequent intraindividual differences between eGFRcys and eGFRcr, and these differences can be used to forecast the risk of CA-AKI.

Biochemical characterization, structure-guided mutagenesis, and application of a recombinant D-allulose 3-epimerase from Christensenellaceae bacterium for the biocatalytic production of D-allulose.

D-Allulose has become a promising alternative sweetener due to its unique properties of low caloric content, moderate sweetness, and physiological effects. D-Allulose 3-epimerase (DAEase) is a promising enzyme for D-Allulose production. However, the low catalytic efficiency limited its large-scale industrial applications. To obtain a more effective biocatalyst, a putative DAEase from Christensenellaceae bacterium (CbDAE) was identified and characterized. The recombinant CbDAE exhibited optimum activity at pH 7.5°C and 55°C, retaining more than 60% relative activity from 40°C to 70°C, and the catalytic activity could be significantly increased by Co2+ supplementation. These enzymatic properties of purified CbDAE were compared with other DAEases. CbDAE was also found to possess desirable thermal stability at 55°C with a half-life of 12.4 h. CbDAE performed the highest relative activity towards D-allulose and strong affinity for D-fructose but relatively low catalytic efficiency towards D-fructose. Based on the structure-guided design, the best double-mutation variant G36N/W112E was obtained which reached up to 4.21-fold enhancement of catalytic activity compared with wild-type (WT) CbDAE. The catalytic production of G36N/W112E with 500 g/L D-fructose was at a medium to a higher level among the DAEases in 3.5 h, reducing 40% catalytic reaction time compared to the WT CbDAE. In addition, the G36N/W112E variant was also applied in honey and apple juice for D-allulose conversion. Our research offers an extra biocatalyst for D-allulose production, and the comprehensive report of this enzyme makes it potentially interesting for industrial applications and will aid the development of industrial biocatalysts for D-allulose.

Fetal growth restriction exhibits various mTOR signaling in different regions of mouse placentas with altered lipid metabolism.

Fetal growth restriction (FGR) is a common complication of pregnancy and can have significant impact on obstetric and neonatal outcomes. Increasing evidence has shown that the inhibited mechanistic target of rapamycin (mTOR) signaling in placenta is associated with FGR. However, interpretation of existing research is limited due to inconsistent methodologies and varying understanding of the mechanism by which mTOR activity contributes to FGR. Hereby, we have demonstrated that different anatomic regions of human and mouse placentas exhibited different levels of mTOR activity in normal compared to FGR pregnancies. When using the rapamycin-induced FGR mouse model, we found that placentas of FGR pregnancies exhibited abnormal morphological changes and reduced mTOR activity in the decidual-junctional layer. Using transcriptomics and lipidomics, we revealed that lipid and energy metabolism was significantly disrupted in the placentas of FGR mice. Finally, we demonstrated that maternal physical exercise during gestation in our FGR mouse model was associated with increased fetal and placental weight as well as increased placental mTOR activity and lipid metabolism. Collectively, our data indicate that the inhibited placental mTOR signaling contributes to FGR with altered lipid metabolism in mouse placentas, and maternal exercise could be an effective method to reduce the occurrence of FGR or alleviate the adverse outcomes associated with FGR.