Individualized dosing parameters for tacrolimus in the presence of voriconazole: a real-world PopPK study.

Objectives: Significant increase in tacrolimus exposure was observed during co-administration with voriconazole, and no population pharmacokinetic model exists for tacrolimus in renal transplant recipients receiving voriconazole. To achieve target tacrolimus concentrations, an optimal dosage regimen is required. This study aims to develop individualized dosing parameters through population pharmacokinetic analysis and simulate tacrolimus concentrations under different dosage regimens. Methods: We conducted a retrospective study of renal transplant recipients who were hospitalized at the Second Xiangya Hospital of Central South University between January 2016 and March 2021. Subsequently, pharmacokinetic analysis and Monte Carlo simulation were employed for further analysis. Results: Nineteen eligible patients receiving tacrolimus and voriconazole co-therapy were included in the study. We collected 167 blood samples and developed a one-compartment model with first-order absorption and elimination to describe the pharmacokinetic properties of tacrolimus. The final typical values for tacrolimus elimination rate constant (Ka), apparent volume of distribution (V/F), and apparent oral clearance (CL/F) were 8.39 h-1, 2690 L, and 42.87 L/h, respectively. Key covariates in the final model included voriconazole concentration and serum creatinine. Patients with higher voriconazole concentration had lower tacrolimus CL/F and V/F. In addition, higher serum creatinine levels were associated with lower tacrolimus CL/F. Conclusion: Our findings suggest that clinicians can predict tacrolimus concentration and estimate optimal tacrolimus dosage based on voriconazole concentration and serum creatinine. The effect of voriconazole concentration on tacrolimus concentration was more significant than serum creatinine. These findings may inform clinical decision-making in the management of tacrolimus and voriconazole therapy in solid organ transplant recipients.

[An efficient and practical electrode optimization method for transcranial electrical stimulation].

Transcranial electrical stimulation (TES) is a non-invasive neuromodulation technique with great potential. Electrode optimization methods based on simulation models of individual TES field could provide personalized stimulation parameters according to individual variations in head tissue structure, significantly enhancing the stimulation accuracy of TES. However, the existing electrode optimization methods suffer from prolonged computation times (typically exceeding 1 d) and limitations such as disregarding the restricted number of output channels from the stimulator, further impeding their clinical applicability. Hence, this paper proposes an efficient and practical electrode optimization method. The proposed method simultaneously optimizes both the intensity and focality of TES within the target brain area while constraining the number of electrodes used, and it achieves faster computational speed. Compared to commonly used electrode optimization methods, the proposed method significantly reduces computation time by 85.9% while maintaining optimization effectiveness. Moreover, our method considered the number of available channels for the stimulator to distribute the current across multiple electrodes, further improving the tolerability of TES. The electrode optimization method proposed in this paper has the characteristics of high efficiency and easy operation, potentially providing valuable supporting data and references for the implementation of individualized TES.

Enzymatic acylation of cyanidin-3-O-glucoside with aromatic and aliphatic acid methyl ester: Structure-stability relationships of acylated derivatives.

Anthocyanins are water-soluble pigments, but they tend to be unstable in aqueous solutions. Modification of their molecular structure offers a viable approach to alter their intrinsic properties and enhance stability. Aromatic and aliphatic acid methyl esters were used as acyl donors in the enzymatic acylation of cyanidin-3-O-glucoside (C3G), and their analysis was conducted using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). The highest conversion rate achieved was 96.41 % for cyanidin-3-O-(6″-feruloyl) glucoside. Comparative evaluations of stability revealed that aromatic acyl group-conjugated C3G exhibited superior stability enhancement compared with aliphatic acyl group derivatives. The stability of aliphatic C3G decreased with increasing carbon chain length. The molecular geometries of different anthocyanins were optimized, and energy level calculations using density functional theory (DFT) identified their sites with antioxidant activities. Computational calculations aligned with the in vitro antioxidant assay results. This study provided theoretical support for stabilizing anthocyanins and broadened the application of acylated anthocyanins as food colorants and nutrient supplements.

Analysis of the implementation effect and evaluation of the vaccine protection effect of the live attenuated varicella vaccine program for school-age children in Bao'an district of Shenzhen,China.

The objective of the study is to analyze the implementation effect of the Live Attenuated Varicella Vaccine (VarV) Vaccination Program for eligible children in Bao'an District, Shenzhen, and evaluate the vaccine effectiveness. Children's vaccination data was obtained from the Shenzhen Immunization Planning Information Management System, while varicella case data came from the China Disease Prevention and Control Information System. The Joinpoint regression method examined vaccination rate trends, and a retrospective cohort study assessed vaccine effectiveness. After program implementation, VarV vaccination rates significantly increased, surpassing provincial and national averages. Overall incidence declined 54.6% across age groups, with the largest reductions among 7- and 6-year-olds. One year post-vaccination, single-dose vaccine effectiveness was 91.1% (95% CI: 79.2% to 96.2%). However, two doses remained 91.4% effective(95% CI: 89.1% to 93.2%) after 7 years. Overall, Shenzhen's VarV program achieved positive results. For children under six, routine immunization with two doses of VarV should be strengthened. Furthermore, we recommend that physicians conduct thorough inquiries to ascertain patients' vaccination history and previous varicella infections. This will enable doctors to provide tailored vaccination recommendations based on comprehensive, practical evaluations.

Metal Ion-Induced Acid Hydrolysis Strategy for the One-Step Synthesis of Tough and Highly Transparent Hydrolyzed Polyacrylamide Hydrogels.

Polyacrylamide (PAM) hydrogel is hard to enhance through coordination bonds because amide groups rarely coordinate with metal ions strongly in an aqueous solution. It is known that the aqueous solution of ZrOCl2.8H2O can be strongly acidic depending on its concentration. Consequently, through a facile one-step metal ion-induced acid hydrolysis strategy (MIAHS), tough and highly transparent hydrolyzed PAM physical hydrogels are prepared by using ZrOCl2.8H2O in this work. The formation of the partially hydrolyzed PAM physical hydrogels elucidates that the side reaction of imidization during common acid hydrolysis of PAM can be perfectly overcome because the structure of the Zr(IV) ion and its interaction with amide groups promote selective acidic hydrolysis from amide to carboxyl groups. Compared to most coordination cross-linked hydrogels, which need at least two-step fabrication, the hydrolyzed PAM hydrogel via MIAHS can be obtained by one-step synthesis due to the weak interaction between amide groups and Zr(IV). The obtained PAM hydrogel cross-linked by hydrogen bonds and coordination bond between Zr(IV) and carboxyl is a multibond network (MBN) and can achieve hierarchical energy dissipation, which exhibits excellent mechanical properties (tensile strength of 3.15 MPa, elongation at break of 890%, and toughness of 17.0 MJ m-3), high transparence (transmittance of 95%), and outstanding conductivity (5.6 S m-1) at water content of 80 wt %. The high gauge factor (from 2.24 to 12.8 as the strain increases from 0 to 400%) endows the hydrolyzed PAM hydrogels with promising application as strain sensors. Furthermore, in addition to ZrOCl2.8H2O, the fact that various hydrolyzable compounds of Ti(IV), Zr(IV) Hf(IV), and Sn(IV) can also fabricate tough hydrolyzed PAM hydrogels verifies the universality of MIAHS. Therefore, the simple, efficient, and universal MIAHS will shed new light on preparing functional PAM-based hydrogels.

Study on vertical variation characteristics of soil phosphorus adsorption and desorption in black soil region of Northeast China.

The adsorption and desorption of phosphorus (P) in soil constitute a crucial internal cycle that is closely associated with soil fertility, exerting direct influence on the quantity, form, and availability of P within the soil. The vertical spatial variation characteristics of soil adsorption and desorption were investigated for the 0-100 cm soil layer in the northeast black soil region in this study. The maximum adsorption capacity (Qmax) and maximum adsorption buffer capacity (MBC) of black soil in the study area ranged from 313.8 to 411.9 mg kg-1 and from 3.1 to 28.8 L kg-1, respectively, within the soil layer of 0-100 cm depth, exhibiting an increasing trend with greater soil depth. The degree of P adsorption saturation (DPS) exhibited a contrasting trend with the variations in Qmax and MBC, ranging from 3.8% to 21.6%. The maximum desorption capacity (Dmax) and desorption rate (Dr) of soil P ranged from 112.8 to 215.7 mg kg-1 and 32.1% to 52.5%, respectively, while the readily desorbable P (RDP) in soil was within the range of 1.02 to 3.35 mg kg-1. Both Dmax, Dr, and RDP exhibited a decreasing trend with increasing soil depth before showing an upward trend. These research findings not only provide essential background data for the systematic investigation of soil P in the black soil region but also serve as a valuable reference for assessing soil quality in this area.

Exploring the therapeutic potential of porphyran extracted from Porphyra haitanensis in the attenuation of DSS-induced intestinal inflammation.

Ulcerative colitis is a chronic, spontaneous inflammatory bowel disease that primarily affects the colon. This study aimed to explore how Porphyra haitanensis porphyran (PHP) modulates the immune response and the associated mechanisms that alleviate dextran sulphate sodium-induced colitis in mice. Histological assessments via H&E staining and AB-PAS staining revealed that PHP intervention partially restored the number of goblet cells and improved intestinal mucosal function. Immunohistochemical and Western blot analyses of claudin-1, occludin, and MUC-2 demonstrated that PHP could repair the intestinal barrier and reduce colon damage by upregulating the expression of these proteins. PHP intervention was associated with a decrease in pro-inflammatory cytokine expression and an increase in anti-inflammatory cytokine expression. Moreover, the expression of proteins involved in intestinal immune homing, such as CCR-9, CCL-25, MAdCAM-1, and α4ß7, was significantly suppressed in response to PHP treatment. Conversely, PHP upregulates the expression of CD40 and TGF-ß1, both of these can promote healing and reduce inflammation in the gut lining. This study demonstrates that PHP can ameliorate ulcerative colitis by enhancing the intestinal barrier and modulating immune responses. These findings offer valuable insights into the potential utility of P. haitanensis as a promising natural product for managing ulcerative colitis.

Optical design of low-location illumination based on asymmetric double freeform surfaces.

The development of optical optics for low-location road lighting is a challenging problem in providing high luminance and uniformity of illumination and meeting many other specific requirements. This study proposes an optical design method of low-location illumination based on an asymmetric double freeform surface lens. The ray emitted from the light source is refracted and reflected through the different surface types to the corresponding area of the receiving surface. In the design example, the road has dual-side mounted luminaires and a width of 6 m, and a height of 0.8 m. Simulation results indicate that, compared with conventional high-pole streetlights, the luminance uniformity had increased from 0.60 to 0.66, the illuminance uniformity had improved from 0.75 to 0.86, and the glare had been reduced.

[Simulation model of tumor-treating fields].

Tumor-treating fields (TTFields) is a novel treatment modality for malignant solid tumors, often employing electric field simulations to analyze the distribution of electric fields on the tumor under different parameters of TTFields. Due to the present difficulties and high costs associated with reproducing or implementing the simulation model construction techniques, this study used readily available open-source software tools to construct a highly accurate, easily implementable finite element simulation model for TTFields. The accuracy of the model is at a level of 1 mm 3. Using this simulation model, the study carried out analyses of different factors, such as tissue electrical parameters and electrode configurations. The results show that factors influncing the distribution of the internal electric field of the tumor include changes in scalp and skull conductivity (with a maximum variation of 21.0% in the treatment field of the tumor), changes in tumor conductivity (with a maximum variation of 157.8% in the treatment field of the tumor), and different electrode positions and combinations (with a maximum variation of 74.2% in the treatment field of the tumor). In summary, the results of this study validate the feasibility and effectiveness of the proposed modeling method, which can provide an important reference for future simulation analyses of TTFields and clinical applications.

The Effect of Colloidal Nanoparticles on Phase Separation of Block and Heteroarm Star Copolymers Confined between Polymer Brushes.

The effect of colloidal nanoparticles on the phase changes of the amphiphilic AB linear diblock, A1A2B, and A2B heteroarm star copolymers confined between two polymer brush substrates was investigated by using a real-space self-consistent field theory. By changing the concentrations of nanoparticles and polymer brushes, the phase structure of the amphiphilic AB copolymer transforms from lamellar to core-shell hexagonal phase to cylinder phase. The pattern of A2B heteroarm star copolymer changes from core-shell hexagonal phases to lamellar phases and the layer decreases when increasing the density of the polymer brushes. The results showed that the phase behavior of the system is strongly influenced by the polymer brush architecture and the colloidal nanoparticle numbers. The colloidal nanoparticles and the soft confined surface of polymer brushes make amphiphilic AB copolymers easier to form ordered structures. The dispersion of the nanoparticles was also investigated in detail. The soft surfaces of polymer brushes and the conformation of the block copolymers work together to force the nanoparticles to disperse evenly. It will give helpful guidance for making some new functional materials by nano etching technology, nano photoresist, and nanoprinting.

Deep eutectic solvent-based ultrasound-assisted extraction in soil samples preparation and elemental determination by ICP-OES.

A fast, simple and green method was established for the extraction of Al, Be, Ca, Co, Cr, Cu, Mn, P, Pb, V and Zn from soil samples using ultrasound-assisted deep eutectic solvents (DESs). DESs based on choline chloride, carboxylic acids and polyols were investigated. It was established that the solvent synthesized from choline chloride and oxalic acid provided the highest extraction recovery (85-104%). Inductively coupled plasma-optical emission spectrometry (ICP-OES) was employed to determine the target analytes in the extracts. The parameters that affect the extraction of target analytes was optimized using standard reference samples. Target analytes could be effectively isolated from soil samples using 0.5 g of DES, ultrasound for 40 min, and heating at 80 â„ƒ. The content of the target analytes determined by this method showed no significant difference from the certified values of 24 reference samples. The proposed method was applied to quantify target analytes in real soil samples. Compared to the traditional acid digestion method, this method showed no significant difference in precision and accuracy, with a confidence level of 95%. The proposed method was found to be simple, accurate and environmentally friendly.

An Operational Approach for Optimizing Transcranial Direct Current Stimulation.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has been utilized for treating brain disorders and improving cognitive function. In order to achieve targeted tDCS, many optimization methods of montages and electric currents have been proposed. However, these methods have some limitations. Most of them were proposed for single-objective optimization (focality or intensity) and have no constrain with the number of electrodes (Most devices only have less than 8 electrodes currently). In this study, we proposed an operational optimization approach for well-targeted tDCS, which aims to optimize for two objectives of electric field (EF) intensity and focality with constraints on the number of electrodes. Compared with traditional tDCS in our cohort (10 subjects), our method significantly improves the EF focality. When compared to commonly used 4×1 high-definition tDCS (HD-tDCS), our method can achieve higher EF intensity in the target region with less than 8 electrodes. Our method can balance the two objectives of EF and shorten optimization time, which is convenient for practical application.

Inactivated SARS-CoV-2 Vaccine Booster Against Omicron Infection Among Quarantined Close Contacts.

Importance: Assessment of additional protection of a booster dose with an inactivated SARS-CoV-2 vaccine is key to developing vaccination strategies for billions of people worldwide who have received the primary 2-dose regimen. Objective: To estimate the relative effectiveness of a booster dose of an inactivated SARS-CoV-2 vaccine against Omicron infection. Design, Setting, and Participants: This cohort study was conducted among primary close contacts without previous SARS-CoV-2 infection identified in Shenzhen, China, between February and October 2022. Multiple strict nucleic acid testing and symptom surveillance for SARS-CoV-2 infection were regularly conducted during the 7-day centralized plus 7-day home-based quarantine. Exposure: A booster with an inactivated SARS-CoV-2 vaccine vs no booster after receipt of the primary 2-dose inactivated SARS-CoV-2 vaccine regimen. Main Outcomes and Measures: The primary outcomes were overall, symptomatic, and asymptomatic infections. Secondary outcomes were length of incubation and level of cycle threshold values. All the outcomes were assessed during the quarantine period. Results: Among 119 438 eligible participants (mean [SD] age, 37.6 [12.0] years; 66 201 men [55.4%]), 86 251 (72.2%) received a booster dose of an inactivated SARS-CoV-2 vaccine and 33 187 (27.8%) did not. A total of 671 cases infected with Omicron BA.2 were confirmed (464 symptomatic and 207 asymptomatic), and no severe infection or death events were observed. At a median (IQR) duration of 111 (75 to 134) days after booster vaccination, the relative effectiveness of a booster was 32.2% (95% CI, 11.3% to 48.2%) for overall infection, 23.8% (95% CI, -8.2% to 46.4%) for symptomatic infection, and 43.3% (95% CI, 12.3% to 63.3%) for asymptomatic infection. The effectiveness against overall infection changed nonlinearly over time following booster vaccination: 44.9% (95% CI, 4.9% to 68.1%) within 60 days, 50.4% (95% CI, 23.7% to 67.7%) at 61 to 120 days, 29.1% (95% CI, -4.8% to 52.1%) at 121 to 180 days, and 19.4% (95% CI, -14.4% to 43.2%) after 180 days (nonlinear P = .03). The effectiveness did not vary significantly according to the interval between booster vaccination and completion of primary vaccination. There was no association of booster vaccination with incubation or cycle threshold values. Conclusions and Relevance: In this cohort study, a booster dose of an inactivated SARS-CoV-2 vaccine provided additional moderate protection against mild infection for 120 days after receipt, but more research is needed to determine the optimal timing of a booster and its effectiveness in preventing severe infection for a longer duration.

Highly Conductive Polysiloxane Elastomers with Excellent Transparency, Resilience, and Stretchability.

Flexible transparent conductive materials show great potential in wearable electronics, flexible sensors, and so on. But the most used flexible conductive materials like hydrogels and ionogels suffer from evaporation and solvent leakage. For the application in these fields, integrated performances of preeminent resilience, transparency, stability, and conductivity that do not change with deformation are prerequisites. It is still challenging to handle the trade-off among these performances. Herein, a facile approach is established to balance these properties into one elastomer. Through the thiol-ene click reaction, mercaptopropyl-modified polydimethylsiloxane (mPDMS) is cross-linked and grafted by PEG-based macromonomers to prepare conductive elastomers. By anchoring with mPDMS through carbon-sulfur bonds, PEG can be evenly dispersed, resulting in ultratransparency (97%) and stable conductivity of as high as 1.68 × 10-2 S m-1, comparable to pure PEG/lithium salt conductivity. It also has a wide electrochemical stability window with a high voltage of 4.8 V. Moreover, the multibond network strategy is employed through grafting ligand 1-vinylimidazole to mPDMS to construct dynamic cross-links between Zn(II) and 1-vinylimidazol, bestowing excellent properties to the elastomers. Overall, elastomers with a well-balanced performance of high resilience, good conductivity, and ultratransparency are obtained, providing promising applications for soft electronics, lithium battery electrolytes, and flexible devices.

One-Step in Situ Synthesis of Tough and Highly Conductive Ionohydrogels with Water-Retentive and Antifreezing Properties.

Flexible and conductive gels are promising materials as intelligent and wearable electronics. Herein, through a facile one-step in situ free-radical polymerization, tough VSNPs-PAA-Zr4+ ionohydrogels with integrated multiple functionalities are prepared, which are dually cross-linked by multivalent vinyl-functionalized silica nanoparticles (VSNPs) and metal coordination between Zr4+ and the carboxyl groups in PAA chains. The incorporation of Zr4+ with stable valency during polymerization enables the direct formation of a large number of metal coordination cross-links for adequate energy dissipation, overcoming the inhibition of unstable metal ions on the polymerization process. Meanwhile, VSNPs serve as multivalent cross-linkers and effective stress transfer centers. The obtained VSNPs-PAA-Zr4+ ionohydrogels show high toughness of up to 25 MJ m-3 with a high tensile strength of 3010 kPa and a large elongation at break of 1360%, along with reliable adhesive performance. Attributed to use of an IL/water binary solvent, the ionohydrogels possess excellent water-retentive and antifreezing abilities. Moreover, the existence of large quantities of mobile ions endows the VSNPs-PAA-Zr4+ ionohydrogels with a superior conductivity of 4.77 S m-1 and a high strain sensitivity with a gauge factor (GF) of 9.04, which are promising materials as intelligent and wearable strain sensors.

Observation of the effect of angiojet to treat acute lower extremity arterial embolization.

BACKGROUND: Through significant advances in the treatment of peripheral arterial occlusive disease, acute ischemia of the lower extremity is still associated with significant morbidity, limb threat and mortality. The two main causes of acute ischemia in lower extremities are arterial embolism and atherosclerotic arteries. Timely recognition and treatment of acute limb ischemia in emergency situations is essential in order to minimize the duration of ischemia. AIM: To investigate the application effect of angiojet thrombolysis in the treatment of acute lower extremity arterial embolization. METHODS: Sixty-two patients with acute lower extremity arterial embolization admitted to our hospital from May 2018 to May 2020 were selected. Among them, the observation group (twenty-eight cases) had received angiojet thrombolysis, and the control group (thirty-four cases) had received femoral artery incision and thrombectomy. After thrombus clearance, significant residual stenosis of the lumen was combined with balloon dilation and/or stent implantation. When the thrombus removal was not satisfactory, catheter-directed thrombolysis was performed. The incidence of postoperative complications, recurrence rate and recovery of the two groups were compared. RESULTS: There were no significant differences in postoperative recurrence (target vessel reconstruction rate), anklebrachial index and the incidence of postoperative complications between the two groups (P > 0.05); there were statistically significant differences in postoperative pain score and postoperative rehabilitation between the two groups (P < 0.05). CONCLUSION: The application of angiojet in the treatment of acute lower limb artery thromboembolism disease is safe and effective, minimally invasive, quicker recovery after operation, less postoperative complications, which is more suitable for the treatment of femoral popliteal arterial thromboembolism lesions. If the thrombus removal is not satisfactory, the combination of coronary artery aspiration catheter and catheterized directed thrombolysis can be used. Balloon dilation and stent implantation can be considered for obvious lumen stenosis.

An investigation on cervical cancer and human papillomavirus vaccine knowledge, and analysis of influencing factors for choosing domestic or imported 2vHPV vaccine among females in Shenzhen, China.

In 2020, the domestic (Chinese native) 2v human papillomavirus (HPV) vaccine was approved for use in females. At present, there are obvious differences in demand for different HPV vaccines. We aimed to investigate knowledge level of cervical cancer and HPV vaccine and its influencing factors among the eligible female recipients in Shenzhen, China, and to analyze the factors influencing choice of 2vHPV vaccine (domestic or imported) would be selected. A self-administered questionnaire was carried out on this investigation, and respondents were selected by random sampling method conducted by vaccination doctors. A total of 1197 valid questionnaires were collected, of which 729 (60.9%) were vaccinated with domestic vaccines and 468 (39.1%) were vaccinated with imported. Four hundred and fifty (61.7%) and 306 (65.4%) got a passing grade, respectively (χ2 = 1.637, P = .201). Logistic regression analysis showed that age (P = .002), ethnicity (P < .001), duration of residence in Shenzhen (P < .001), educational level (P < .001) and occupation (P < .001) were significant. It also showed that the manufacturers (P < .001), efficacy (P < .001), safety (P < .001), cognitive approach (P < .001), public opinion (P < .001), convenient acquisition (P < .001) and knowledge reserve (P = .035) were statistically significant. While price (P = .371) and doctor's suggestion (P = .114) were not. In conclusion, eligible female recipients had a high degree of knowledge regarding cervical cancer and HPV vaccine, education level and occupation were the most important factors for scores. Domestic 2vHPV vaccine was more widely utilized than imported, manufacturer, efficacy, safety, cognitive approach, public opinion, convenient acquisition, and knowledge reserve had an impact on selection for recipients, while price and doctor's suggestion did not.

Effects of Ruxolitinib on Myeloproliferative Neoplasms via the Negative Regulators.

BACKGROUND: We evaluated the JAK2V617F mutation and p-JAK2, SOCS-1, SHP-1 expression in JAK2V617F positive myeloproliferative neoplasms (MPNs) patients and the role of JAK/STAT pathway in human erythroleukemia (HEL) cells, which had JAK2V617F mutation. METHODS: Protein expression of p-JAK2, SOCS-1, SHP-1 in bone marrow biopsies (BMBs) were detected by immunohistochemical staining methods. Cell apoptosis and cell cycle were detected by flow cytometry and Caspase 3/7 assay kits. RESULTS: 1. The p-JAK2, SOCS-1, and SHP-1 expressions were significantly different between JAK2V617F positive MPN and control patients (p < 0.01); 2. After being treated for 3 months, the p-JAK2, SOCS-1, and SHP-1 expressions were significantly different compared with newly diagnosed patients (p < 0.01). 3. HEL cell viabilities were significantly different after being treated with different concentrations of ruxolitinib. Ruxolitinib had a significant effect on the cell apoptosis, viability, and the protein activity of caspase-3 and -7 of HEL cells. 3. The mRNA and protein expressions of JAK2 and the protein expression of p-JAK2 were gradually decreased (p ＜ 0.01, p ＜ 0.05), while the mRNA and protein expressions of SOCS1 and SHP1 were gradually increased (all p ＜ 0.01).

Seawall-induced impacts on large river delta wetlands and blue carbon storage under sea level rise.

Coastal wetlands have been enclosed by thousands of kilometers of seawalls in China to obtain extra land for rapid socio-economic development in the coastal region. Although understanding seawall-induced impacts on delta wetlands and their ecosystem can provide valuable decision-making information to support coastal management, quantifying and measuring long-term, cumulative ecological impacts of harden seawall under sea level rise (SLR) remains a vital research gap. In this study, by combining the land-use transformation trajectory analysis, ecosystem services assessment, and the SLAMM (Sea Level Affecting Marshes Model), we have explored the seawall-induced effects on temporal-spatial dynamics of tidal wetlands and the Coastal Blue Carbon storage (CBCs) in the Yellow River Delta (YRD) under the SLR by 2050 and 2100. Our study revealed that the delta wetland area would have increased by 2327.87 km2 after seawall removal without regard for SLR while increasing by 3050 km2 in 2100 in both seawall scenarios under SLR. The effects of driving processes trajectory on the changes in CBCs indicated two-sided seawall-induced impacts on the delta wetlands in the YRD, i.e., functioning as a physical coastal defense to prevent coastal erosion (before 2050) while intensifying coastal squeeze effects and quickening the loss in delta wetlands and the CBCs by hindering their inland migration under SLR. For example, the gap of CBCs between the seawall-impacting and seawall-removal scenarios would have reached at 9.94 × 106 Mg by 2050 under the SLR, and the magnitude of the final decrease effect on CBCs induced by the seawall-impacting would be nearly 5 times higher than its gain after seawall-removal in the regressive succession, while the same magnitudes in the salinization process on both scenarios. Our study has provided valuable insights for shoreline management by mitigating seawall-induced impacts on the delta wetlands and their ecosystem services such as CBCs.

Protein Kinase CK2 Modulates the Calcium Sensitivity of Type 3 Small-conductance Calcium-activated Potassium Channels in Colonic Platelet-derived Growth Factor Receptor Alpha-positive Cells From Streptozotocin-induced Diabetic Mice

Background/Aims@#The gastrointestinal symptom of diabetes mellitus, chronic constipation, seriously affects patients’ life. Whereas, the mechanism of chronic constipation is still ambiguous, resulting in a lack of effective therapies for this symptom. As a part of the smooth muscle cells, interstitial cells of Cajal, and platelet-derived growth factor receptor alpha-positive (PDGFRα+ ) cells syncytium (SIP syncytium), PDGFRα+ cells play an important role in regulating colonic motility. According to our previous study, in PDGFRα+cells in colons of diabetic mice, the function of the P2Y1 purinergic receptor/type 3 small-conductance calcium-activated potassium (SK3) channel signaling pathway is strengthened, which may lead to colonic dysmotility. The purpose of this study is to investigate the changes in SK3 channel properties of PDGFRα+ cells in diabetic mice. @*Methods@#Whole-cell patch clamp, Western blotting, superoxide dismutase activity measurement, and malondialdehyde measurement were main methods in the present study. @*Results@#The present study revealed that when dialysed with low calcium ion (Ca 2+ ) solution, the SK3 current density was significantly decreased in PDGFRα+ cells from diabetic mice. However, the SK3 current density in PDGFRα+ cells was enhanced from diabetic mice when dialysed with high Ca 2+ solution. Moreover, hydrogen peroxide-treatment mimicked this phenomenon in SK3 transgenic HEK293 cells. The subunit of SK3 channels, protein kinase CK2, was up-regulated in colonic muscle layers and hydrogen peroxidetreated HEK293 cells. Additionally, protein phosphatase 2A, the subunit of SK3 channels, was not changed in streptozotocin-treated mouse colons or hydrogen peroxide-treated HEK293 cells. @*Conclusion@#The diabetic oxidative stress-induced upregulation of CK2 contributed to modulating SK3 channel sensitivity to Ca 2+ in colonic PDGFRα+ cells, which may result in colonic dysmotility in diabetic mice.