A primary battery for efficient cadmium contamination remediation and electricity generation.

In this work, two kinds of primary batteries, both of which included a Zn anode, C rod cathode, copper wire and electrolyte composed of Cd2+-contaminated water or soil, were constructed in the first attempt to both remove Cd2+ and generate electricity. Unlike traditional technologies such as electrokinetic remediation with high energy consumption, this technology could realize Cd2+ migration to aggregation and solidification and generate energy at the same time through simultaneous galvanic reactions. The passive surface of Zn and C was proven via electrochemical measurements to be porous to maintain the relatively active galvanic reactions for continuous Cd2+ precipitation. Cd2+ RE (removal efficiency) and electricity generation were investigated under different conditions, based on which two empirical models were established to predict them successfully. In soil, KCl was added to desorb Cd2+ from soil colloids to promote Cd2+ removal. These systems were also proven to remove Cd2+ efficiently when their effects on plants, zebrafish, and the soil bacterial community were tested. LEDs could be lit for days by utilizing the electricity produced herein. This work provides a novel, green, and low-cost route to remediate Cd2+ contamination and generate electricity simultaneously, which is of extensive practical significance in the environmental and energy fields.

Effect of potassium chloride-induced salt stress on bacoside A biosynthesis in Bacopa monnieri (L.) grown under in vitro and in vivo conditions: a comparative study.

Bacopa monnieri L. is a highly acclaimed plant species for its diverse pharmaceutical properties and is mostly found in the Indian subcontinent. In this study, the effects of salt (KCl) stress on plant height, biomass, chlorophyll content, and antioxidant enzyme activities of Bacopa monnieri in both in vitro and in vivo conditions were investigated. A significant increase of up to 1.8 folds and 1.3 folds in bacoside-A content at 100 mM KCl was recorded in both in vivo and in vitro grown plants, respectively. Higher salinity (> 100 mM KCl) stress exerted a negative effect on plant height and plant biomass, whereas at levels ≤ 100 KCl, substantial improvement in terms of plant height (PH) and biomass (PB) was recorded in both in vivo (up to 1.6-fold and 1.8-fold high) and in vitro (up to 1.9-fold and 1.7-fold high) conditions. Total chlorophyll content and antioxidant enzyme (CAT, POD) activities were also maximum at 100 mM KCl. However, at higher KCl levels (200 mM), no significant increase in any of the morphophysiological parameters was recorded. Therefore, 100 mM KCl was identified as the optimum salt concentration for enhancing bacoside A content, plant growth, and physiological properties in terms of antioxidant enzyme activity and chlorophyll content in B. monnieri.

Trans-abdominal fetal reduction in higher order multiple pregnancies: a pioneer cohort retrospective study in Nepal.

Objective: To share the initial experience of trans-abdominal multifetal pregnancy reduction (MFPR) in Nepal. Method: The procedure was performed in 108 patients in a private hospital over a period of 3 years. Under ultrasound guidance, intracardiac injection of 0.2-3.0 ml of 15% w/v (2 mEq/ml) potassium chloride (KCl) was administered via trans-abdominal route. Results: A total of 108 fetal reduction procedures were carried out at the seventh to fifteenth weeks of gestation, a maximum of 44 (40.7%) of which were done at the ninth to tenth weeks of gestation. A total of 123 fetuses were reduced. Out of total 108 multifetal pregnancies, 96 (88.8%) were due to in-vitro fertilization (IVF). Eighty-five pregnancies (78.7%) underwent reduction from triplet to twin. The second-time reduction was needed in five cases. Two attempts (in the same sitting) were required in three cases. The inadvertent demise of the second fetus was noted in three cases of dichorionic tri-amniotic triplet pregnancy. Conclusion: Ultrasound-guided trans-abdominal fetal reduction performed between the seventh and twelfth weeks of gestation is safe and effective.

Effect of Lipopolysaccharide on the Duration of Zolpidem-Induced Loss of Righting Reflex in Mice.

Zolpidem, a non-benzodiazepine hypnotic, is primarily used to treat insomnia. In a previous study, pior treatment with non-benzodiazepine receptor agonists was associated with inflammation. The present study aimed to clarify the association between the effects of zolpidem and inflammation in mice treated with lipopolysaccharide (LPS), a known model of inflammation. We assessed the zolpidem-induced loss of righting reflex (LORR) duration 24 h after LPS treatment in mice. Additionally, the expressions of γ-aminobutyric acid (GABA)A receptor subunit and K+-Cl- cotransporter isoform 2 (KCC2) mRNA in the hippocampus and frontal cortex were examined in LPS-treated mice. Pretreatment with LPS was associated with significantly prolonged duration of zolpidem-induced LORR compared to control mice. This effect was significantly attenuated by administering bicuculline, a GABAA receptor antagonist, or flumazenil, a benzodiazepine receptor antagonist, in LPS-treated mice. Compared to controls, LPS-treated mice showed no significant change in the expression of GABAA receptor subunits in the hippocampus or frontal cortex. Bumetanide, an Na+-K+-2Cl- cotransporter isoform 1 blocker, attenuated the extended duration of zolpidem-induced LORR observed in LPS-treated mice. LPS significantly decreased Kcc2 mRNA expression in the hippocampus and the frontal cortex. These findings suggest that inflammation increases zolpidem-induced LORR, possibly through a reduction in KCC2 expression.

Focal brain cooling suppresses spreading depolarization and reduces endothelial nitric oxide synthase expression in rats.

This study aimed to investigate the effects of focal brain cooling (FBC) on spreading depolarization (SD), which is associated with several neurological disorders. Although it has been studied from various aspects, no medication has been developed that can effectively control SD. As FBC can reduce neuronal damage and promote functional recovery in pathological conditions such as epilepsy, cerebral ischemia, and traumatic brain injury, it may also potentially suppress the onset and progression of SD. We created an experimental rat model of SD by administering 1 M potassium chloride (KCl) to the cortical surface. Changes in neuronal and vascular modalities were evaluated using multimodal recording, which simultaneously recorded brain temperature (BrT), wide range electrocorticogram, and two-dimensional cerebral blood flow. The rats were divided into two groups (cooling [CL] and non-cooling [NC]). Warm or cold saline was perfused on the surface of one hemisphere to maintain BrT at 37°C or 15°C in the NC and CL groups, respectively. Western blot analysis was performed to determine the effects of FBC on endothelial nitric oxide synthase (eNOS) expression. In the NC group, KCl administration triggered repetitive SDs (mean frequency = 11.57/h). In the CL group, FBC increased the duration of all KCl-induced events and gradually reduced their frequency. Additionally, eNOS expression decreased in the cooled brain regions compared to the non-cooled contralateral hemisphere. The results obtained by multimodal recording suggest that FBC suppresses SD and decreases eNOS expression. This study may contribute to developing new treatments for SD and related neurological disorders.

Corrosion Behavior of Ni-Cr Alloys with Different Cr Contents in NaCl-KCl-MgCl2.

This study investigates the corrosion behavior of Ni-Cr binary alloys, including Ni-10Cr, Ni-15Cr, Ni-20Cr, Ni-25Cr, and Ni-30Cr, in a NaCl-KCl-MgCl2 molten salt mixture through gravimetric analysis. Corrosion tests were conducted at 700 °C, with the maximum immersion time reaching up to 100 h. The corrosion rate was determined by measuring the mass loss of the specimens at various time intervals. Verifying corrosion rates by combining mass loss results with the determination of element dissolution in molten salts using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). Detailed examinations of the corrosion products and morphology were conducted using X-ray diffraction (XRD) and scanning electron microscopy (SEM). Micro-area elemental analysis on the corroded surfaces was performed using an energy dispersive spectrometer (EDS), and the elemental distribution across the corrosion cross-sections was mapped. The results indicate that alloys with lower Cr content exhibit superior corrosion resistance in the NaCl-KCl-MgCl2 molten salt under an argon atmosphere compared to those with higher Cr content; no corrosion products were retained on the surfaces of the lower Cr alloys (Ni-10Cr, Ni-15Cr). For the higher Cr alloys (Ni-20Cr, Ni-25Cr, Ni-30Cr), after 20 h of corrosion, a protective layer was observed in certain areas. The formation of a stable Cr2O3 layer in the initial stages of corrosion for high-Cr content alloys, which reacts with MgO in the molten salt to form a stable MgCr2O4 spinel structure, provides additional protection for the alloys. However, over time, even under argon protection, the MgCr2O4 protective layer gradually degrades due to chloride ion infiltration and chemical reactions at high temperatures. Further analysis revealed that chloride ions play a pivotal role in the corrosion process, not only facilitating the destruction of the Cr2O3 layer on the alloy surfaces but also possibly accelerating the corrosion of the metallic matrix through electrochemical reactions. In conclusion, the corrosion behavior of Ni-Cr alloys in the NaCl-KCl-MgCl2 molten salt environment is influenced by a combination of factors, including Cr content, chloride ion activity, and the formation and degradation of protective layers. This study not only provides new insights into the corrosion resistance of Ni-Cr alloys in high-temperature molten salt environments but also offers significant theoretical support for the design and optimization of corrosion-resistant alloy materials.

Manganese-Doped Potassium Chloride Nanoelectrodes to Potentiate Electrochemical Immunotherapy.

Hypochlorous acid (HClO), as a powerful oxidizer, is obtained from the oxidation of Cl- ions during the electrochemical therapy (EChT) process for cancer therapy. However, the extracellular generated HClO is inadequate to inhibit effective tumor cell death. Herein, manganese-doped potassium chloride nanocubes (MPC NCs) fabricated and modified with amphipathic polymer PEG (PMPC NCs) to function as massive three-dimensional nanoelectrodes (NEs) were developed to enhance the generation of HClO for electrochemical immunotherapy under an alternating electric field. Under an square-wave alternating current (AC) electric field, the generation of HClO was boosted by PMPC NEs due to the enlarged active surface area, enhanced mass transfer rate, and improved electrocatalytic activity. Notably, PMPC NEs upregulated the intracellular HClO concentration to induce robust immunogenic cell death (ICD) under an AC electric field. Meanwhile, the electric-triggered release of Mn2+ effectively stimulated dendritic cells (DCs) maturation. In vivo results illustrated that PMPC-mediated EChT inhibited tumor growth and triggered the promotion of the immune response to regulate the tumor immune microenvironment. Based on the potent antitumor immunity, PMPC-mediated EChT was further combined with an immune checkpoint inhibitor (αCTLA-4) to realize combined EChT-immunotherapy, which demonstrated enhanced tumor inhibition of the primary tumors and an abscopal effect on distant tumors. To summarize, our work highlights the application of electrochemical-immunotherapy technology in tumor therapy.

Relationship between the severity of pre-frailty and the degree of adaptation of Ninjin'yoeito (NYT) on pre-frailty.

With the global trend towards longer life expectancies, there's an increasing emphasis on not just living longer, but also maintaining health and wellbeing into older age. This study explores the efficacy of Ninjin'yoeito (NYT) in the early stages of frailty, a critical period for preventive interventions. Taking account of the knowledge gap regarding the association between early frailty and NYT, we use data from workplace health checkups to examine the relationship between pre-frailty severity and NYT adaption. The objective of our research is to enhance the comprehension of early treatments using NYT to prevent the progression of frailty. A total of 314 employees of the Kyoto Industrial Health Association who received workplace health checkups between November 2021 and March 2023 and consented to this study were included in the analysis. Information on gender, age, body mass index (BMI), NYT-specific symptoms assessment, the Japanese version of the General Health Questionnaire-12 (GHQ-12), and the Kihon Checklist (KCL) were obtained. The correlation analysis revealed that there was a strong positive correlation between the number of applicable NYT indications and the GHQ-12 score (r = 0.5992, p < 0.0001). Similarly, a moderate positive correlation was observed between the number of applicable NYT indications and the KCL score (r = 0.5030, p < 0.0001). In the multivariate analysis, both GHQ-12 (ß = 0.49, SE = 0.06, t = 7.66, 95% CI: 0.36 to 0.62, p = 0.000) and KCL (ß = 0.54, SE = 0.12, t = 4.29, 95% CI: 0.29 to 0.79, p = 0.000) showed significant positive associations with the variance in the number of applicable NYT indications, indicating that higher scores on these measures were related to a greater number of indications. NYT has the potential to be utilized not only as a therapeutic intervention for frailty, but also as a preventive measure.

Tailorable mechanical and degradation properties of KCl-reticulated and BDDE-crosslinked PCL/chitosan/κ-carrageenan electrospun fibers for biomedical applications: Effect of the crosslinking-reticulation synergy.

The development of intricated and interconnected porous mats is desired for many applications in biomedicine and other relevant fields. The mats that comprise the use of natural, bioactive, and biodegradable polymers are the focus of current research activities. In the present work, crosslinked fibers with improved characteristics were produced by incorporating 1,4-butanediol diglycidyl ether (BDDE) into a polymer formulation containing polycaprolactone (PCL), chitosan (CS), and κappa-carrageenan (κ-C). A slight variation of formic acid (FA)/acetic acid (AA) ratio used as a solvent system, significantly affected the characteristics of the produced fiber mats. Both polysaccharides and BDDE played a major role in tailoring mechanical properties when fibrous scaffolds were reticulated under KCl-mediated basic conditions for determined periods of time at 50 °C. In vitro biological assessment of the electrospun fiber mats revealed proliferation of MC3T3-E1 cells when incubated for 1 and 7 days. After staining the cells with 4',6-diamidino-2-phenylindole (DAPI)/rhodamine phalloidin an autofluorescence response was observed by fluorescence microscopy in the scaffold manufactured using a solvent with higher FA/AA ratio due to the formation of microfibers. The results demonstrated the potential of the BDDE-crosslinked PCL/CS/κ-C electrospun fibers as promising materials for biomedical applications that may include soft and bone tissue regeneration.

Solubilization of fish myofibrillar proteins in NaCl and KCl solutions: A DIA-based proteomics analysis.

Understanding the basic solubilization of fish myofibrillar proteins (MPs) in common monovalent chloride solutions is crucial for muscle food processing. In this study, the differential proteomic profiles of MPs during extraction and solubilization in NaCl and KCl solutions were investigated by using advanced four-dimensional data-independent acquisition (4D DIA) quantitative proteomics for the first time. Compared to routine biochemical analysis, this could provide insights into the solubilization of muscle proteins. We ensure the consistency of the effective ionic strength of NaCl and KCl buffers by adjusting the conductivity. The results showed that NaCl extractor mainly facilitated the solubilization of cytoskeletal proteins, biochemical enzymes, and stromal proteins compared to KCl, such as tubulin, myosin-9, collagen, plectin, protein phosphatase, and cathepsin D. However, no significant difference was observed in the extraction of major sarcomeric proteins, including myosin, actin, troponin C, myosin-binding protein C, M-Protein, α-actinin-3, and tropomyosin.

Hypernegative GABAA Reversal Potential in Pyramidal Cells Contributes to Medial Prefrontal Cortex Deactivation in a Mouse Model of Neuropathic Pain.

Deactivation of the medial prefrontal cortex (mPFC) has been broadly reported in both neuropathic pain models and human chronic pain patients. Several cellular mechanisms may contribute to the inhibition of mPFC activity, including enhanced GABAergic inhibition. The functional effect of GABAA(γ-aminobutyric acid type A)-receptor activation depends on the concentration of intracellular chloride in the postsynaptic neuron, which is mainly regulated by the activity of Na-K-2Cl cotransporter isoform 1 (NKCC1) and K-Cl cotransporter isoform 2 (KCC2), 2 potassium-chloride cotransporters that import and extrude chloride, respectively. Recent work has shown that the NKCC1-KCC2 ratio is affected in numerous pathological conditions, and we hypothesized that it may contribute to the alteration of mPFC function in neuropathic pain. We used quantitative in situ hybridization to assess the level of expression of NKCC1 and KCC2 in the mPFC of a mouse model of neuropathic pain (spared nerve injury), and we found that KCC2 transcript is increased in the mPFC of spared nerve injury mice while NKCC1 is not affected. Perforated patch recordings further showed that this results in the hypernegative reversal potential of the GABAA current in pyramidal neurons of the mPFC. Computational simulations suggested that this change in GABAA reversal potential is sufficient to significantly reduce the overall activity of the cortical network. Thus, our results identify a novel pathological modulation of GABAA function and a new mechanism by which mPFC function is inhibited in neuropathic pain. Our data also help explain previous findings showing that activation of mPFC interneurons has proalgesic effect in neuropathic, but not in control conditions. PERSPECTIVE: Chronic pain is associated with the presence of depolarizing GABAA current in the spinal cord, suggesting that pharmacological NKCC1 antagonism has analgesic effects. However, our results show that in neuropathic pain, GABAA current is actually hyperinhibitory in the mPFC, where it contributes to the mPFC functional deactivation. This suggests caution in the use of NKCC1 antagonism to treat pain.

Neuronal K+-Cl- cotransporter KCC2 as a promising drug target for epilepsy treatment.

Epilepsy is a prevalent neurological disorder characterized by unprovoked seizures. γ-Aminobutyric acid (GABA) serves as the primary fast inhibitory neurotransmitter in the brain, and GABA binding to the GABAA receptor (GABAAR) regulates Cl- and bicarbonate (HCO3-) influx or efflux through the channel pore, leading to GABAergic inhibition or excitation, respectively. The neuron-specific K+-Cl- cotransporter 2 (KCC2) is essential for maintaining a low intracellular Cl- concentration, ensuring GABAAR-mediated inhibition. Impaired KCC2 function results in GABAergic excitation associated with epileptic activity. Loss-of-function mutations and altered expression of KCC2 lead to elevated [Cl-]i and compromised synaptic inhibition, contributing to epilepsy pathogenesis in human patients. KCC2 antagonism studies demonstrate the necessity of limiting neuronal hyperexcitability within the brain, as reduced KCC2 functioning leads to seizure activity. Strategies focusing on direct (enhancing KCC2 activation) and indirect KCC2 modulation (altering KCC2 phosphorylation and transcription) have proven effective in attenuating seizure severity and exhibiting anti-convulsant properties. These findings highlight KCC2 as a promising therapeutic target for treating epilepsy. Recent advances in understanding KCC2 regulatory mechanisms, particularly via signaling pathways such as WNK, PKC, BDNF, and its receptor TrkB, have led to the discovery of novel small molecules that modulate KCC2. Inhibiting WNK kinase or utilizing newly discovered KCC2 agonists has demonstrated KCC2 activation and seizure attenuation in animal models. This review discusses the role of KCC2 in epilepsy and evaluates its potential as a drug target for epilepsy treatment by exploring various strategies to regulate KCC2 activity.

On the thermoluminescence characteristics of NaF and KCl.

Thermoluminescence (TL) properties of NaF and KCl are investigated in order to assess their suitability as radiation dosemeters for retrospective dosimetry. TL measurements were made on samples irradiated to different doses (1-20 Gy) and heated at a rate ranging from 0.4 to 4 °C/s in a TL/OSL reader. The TL glow curves of NaF, readout at 1oCs-1, exhibited six apparent peaks around 38.7 ± 1.4, 63.5 ± 0.5, 105.5 ± 0.4, 237.5 ± 0.8, 299.0 ± 1.0 and 347.5 ± 0.7 °C with a shoulder around 168.0 ± 2.3 °C. Those of KCl have three clearly identifiable peaks around 44.0 ± 0.3, 95.3 ± 0.8 and 160.5 ± 0.7 °C. Glow curve deconvolution, however, revealed that the glow curves of NaF and KCl are best fitted with nine and five glow peaks respectively. In NaF, all the peaks exhibited linearity of dose-response in the entire dose range considered in this study. Only the peaks around 95.3 ± 0.8 and 160.5 ± 0.7 °C exhibited linear dose-response in the entire dose range for KCl. In NaF, there was thermal quenching of the TL responses of the peaks around 63.5 ± 0.5, 105.5 ± 0.4 and 237.5 ± 0.8 °C, and thermal enhancement of responses for peaks around 299.0 ± 1.0 and 347.5 ± 0.7 °C. With respect to KCl, the TL responses of all the peaks exhibited thermal enhancement as heating rate was increased. The activation energies associated with the thermal enhancement and quenching of the peaks' TL responses are presented. The repeated use of an aliquot of NaF five times for dose measurements resulted in an acceptable variation in sensitivity, on the other hand the sensitivity of KCl decreased with increasing number of repeat use. The activation energy of the electron traps associated with the glow peaks in both crystals calculated in this study are comparable to previously published values. Both crystals can be used for retrospective dosimetry however change in sensitivity with repeat use of an aliquot will have to be accounted for in the case of KCl.

KCl Treatment of CdS Electron-Transporting Layer for Improved Performance of Sb2(S,Se)3 Solar Cells.

Antimony sulfoselenide (Sb2(S,Se)3) is a promising light absorption material because of its high photoabsorption coefficient, appropriate band gap, superior stability, and abundant elemental storage. As an emerging solar material, hydrothermal deposition of Sb2(S,Se)3 solar cells has enabled a 10% efficiency threshold, where cadmium sulfide (CdS) is applied as an electron transport layer (ETL). The high-efficiency Sb2(S,Se)3 solar cells largely employ CdS as the ETL. In terms of efficiency improvement, there are two questions regarding the CdS substrate: (1) the high roughness of CdS grown on F-doped tin oxide glass which increases the roughness of the absorber layer and (2) the low conductivity of CdS films because of low purity of CdS film grown by chemical bath deposition. In this study, we demonstrate an effective potassium chloride (KCl) post-treatment to modify the CdS ETL for improving the Sb2(S,Se)3 solar cell efficiency. We found that KCl plays dual roles that reduce roughness and enhance conductivity of the CdS films, thus acquiring a maximum efficiency of 9.98%, which is 9.2% higher than the control device. This study provides a new method for the surface engineering of CdS layer to improve the morphological and electrical properties, which is significant for improving the performance of CdS-based thin-film solar cells.

Partial Replacement of NaCl by KCl, MgCl2 and CaCl2 Chloride Salts in the Production of Sucuk: Effects on Volatile Compounds, Lipid Oxidation, Microbiological and Sensory Properties.

The effects of different chloride salt mixtures (I-control: 100% NaCl, II: 50:50-NaCl:KCl, III: 50:30:20-NaCl:KCl:MgCl2, IV: 50:30:20-NaCl:KCl:CaCl2, V: 50:30:10:10-NaCl:KCl:MgCl2:CaCl2) on the quality properties of sucuk (a dry fermented beef sausage) during ripening were investigated. Lactic acid bacteria reached 8 log cfu/g in the 3 days of fermentation in all treatments. However, salt mixtures including MgCl2 caused an increase in Micrococcus/Staphylococcus. The control group showed the lowest mean aw value at the end of ripening. The salt mixture with 20% CaCl2 showed the lowest mean pH value of 4.97. The mean TBARS value varied between 6.34 and 6.97 µmol MDA/kg but was not affected by the salt mixtures (p > 0.05). According to the results of PCA, salt mixtures I, II and III had a positive correlation in PC1, and PC1 also separated salt mixtures with CaCl2 (IV and V) from other groups. In addition, a strong positive correlation between the control and III group (50:30:20-NaCl:KCl:MgCl2) for sensory properties was determined by heatmap clustering analysis. In addition, the principal component analysis showed that the control, II, and III groups had a stronger correlation with each other for volatile compounds.

Monovalent Salt and pH-Stimulated Gelation of Scallop (Patinopecten yessoensis) Male Gonad Hydrolysates/κ-Carrageenan.

The gelation of scallop Patinopecten yessoensis male gonad hydrolysates (SMGHs) and κ-carrageenan (KC) subjected to pH (2-8, 3-9) and NaCl/KCl stimuli-response was investigated. SMGHs/KC gels subjected to a NaCl response exhibited an increasing storage modulus G'from 2028.6 to 3418.4 Pa as the pH decreased from pH 8 to 2, with corresponding T23 fluctuating from 966.40 to 365.64 ms. For the KCl-treated group, SMGHs/KC gels showed an even greater G' from 4646.7 to 10996.5 Pa, with T23 fluctuating from 622.2 to 276.98 ms as the pH decreased from 9 to 3. The improved gel strength could be ascribed to the blueshift and redshift of hydroxyl groups and amide I peaks, enhanced enthalpy and peak temperature, and gathered characteristic diffraction peaks from SMGHs, KC, NaCl, and KCl. The CLSM and cryo-SEM images further reflected that SMGHs/KC gels showed more flocculation formation and denser and more homogeneous networks with smaller pore sizes in more acidic domains, especially when subjected to the KCl response. This research gives a theoretical and methodological understanding of the construction of salt- and pH-responsive SMGHs/KC hydrogels as novel functional soft biomaterials applied in food and biological fields.

First-trimester cesarean scar pregnancy: a comparative analysis of treatment options from the international registry.

BACKGROUND: A cesarean scar pregnancy is an iatrogenic consequence of a previous cesarean delivery. The gestational sac implants into a niche created by the incision of the previous cesarean delivery, and this carries a substantial risk for major maternal complications. The aim of this study was to report, analyze, and compare the effectiveness and safety of different treatments options for cesarean scar pregnancies managed in the first trimester through a registry. OBJECTIVE: This study aimed to evaluated the ultrasound findings, disease behavior, and management of first-trimester cesarean scar pregnancies. STUDY DESIGN: We created an international registry of cesarean scar pregnancy cases to study the ultrasound findings, disease behavior, and management of cesarean scar pregnancies. The Cesarean Scar Pregnancy Registry collects anonymized ultrasound and clinical data of individual patients with a cesarean scar pregnancy on a secure, digital information platform. Cases were uploaded by 31 participating centers across 19 countries. In this study, we only included live and failing cesarean scar pregnancies (with or without a positive fetal heart beat) that received active treatment (medical or surgical) before 12+6 weeks' gestation to evaluate the effectiveness and safety of the different management options. Patients managed expectantly were not included in this study and will be reported separately. Treatment was classified as successful if it led to a complete resolution of the pregnancy without the need for any additional medical interventions. RESULTS: Between August 29, 2018, and February 28, 2023, we recorded 460 patients with cesarean scar pregnancies (281 live, 179 failing cesarean scar pregnancy) who fulfilled the inclusion criteria and were registered. A total of 270 of 460 (58.7%) patients were managed surgically, 123 of 460 (26.7%) patients underwent medical management, 46 of 460 (10%) patients underwent balloon management, and 21 of 460 (4.6%) patients received other, less frequently used treatment options. Suction evacuation was very effective with a success rate of 202 of 221 (91.5%; 95% confidence interval, 87.8-95.2), whereas systemic methotrexate was least effective with only 38 of 64 (59.4%; 95% confidence interval, 48.4-70.4) patients not requiring additional treatment. Overall, surgical treatment of cesarean scar pregnancies was successful in 236 of 258 (91.5%, 95% confidence interval, 88.4-94.5) patients and complications were observed in 24 of 258 patients (9.3%; 95% confidence interval, 6.6-11.9). CONCLUSION: A cesarean scar pregnancy can be managed effectively in the first trimester of pregnancy in more than 90% of cases with either suction evacuation, balloon treatment, or surgical excision. The effectiveness of all treatment options decreases with advancing gestational age, and cesarean scar pregnancies should be treated as early as possible after confirmation of the diagnosis. Local medical treatment with potassium chloride or methotrexate is less efficient and has higher rates of complications than the other treatment options. Systemic methotrexate has a substantial risk of failing and a higher complication rate and should not be recommended as first-line treatment.

Melatonin enhances KCl salinity tolerance by maintaining K+ homeostasis in Malus hupehensis.

Large amounts of potash fertilizer are often applied to apple (Malus domestica) orchards to enhance fruit quality and yields, but this treatment aggravates KCl-based salinity stress. Melatonin (MT) is involved in a variety of abiotic stress responses in plants. However, its role in KCl stress tolerance is still unknown. In the present study, we determined that an appropriate concentration (100 µm) of MT significantly alleviated KCl stress in Malus hupehensis by enhancing K+ efflux out of cells and compartmentalizing K+ in vacuoles. Transcriptome deep-sequencing analysis identified the core transcription factor gene MdWRKY53, whose expression responded to both KCl and MT treatment. Overexpressing MdWRKY53 enhanced KCl tolerance in transgenic apple plants by increasing K+ efflux and K+ compartmentalization. Subsequently, we characterized the transporter genes MdGORK1 and MdNHX2 as downstream targets of MdWRKY53 by ChIP-seq. MdGORK1 localized to the plasma membrane and enhanced K+ efflux to increase KCl tolerance in transgenic apple plants. Moreover, overexpressing MdNHX2 enhanced the KCl tolerance of transgenic apple plants/callus by compartmentalizing K+ into the vacuole. RT-qPCR and LUC activity analyses indicated that MdWRKY53 binds to the promoters of MdGORK1 and MdNHX2 and induces their transcription. Taken together, our findings reveal that the MT-WRKY53-GORK1/NHX2-K+ module regulates K+ homeostasis to enhance KCl stress tolerance in apple. These findings shed light on the molecular mechanism of apple response to KCl-based salinity stress and lay the foundation for the practical application of MT in salt stress.

Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamic results of KCL-286, a novel retinoic acid receptor-ß agonist for treatment of spinal cord injury, in male healthy participants.

AIMS: KCL-286 is an orally available agonist that activates the retinoic acid receptor (RAR) ß2, a transcription factor which stimulates axonal outgrowth. The investigational medicinal product is being developed for treatment of spinal cord injury (SCI). This adaptive dose escalation study evaluated the tolerability, safety and pharmacokinetics and pharmacodynamic activity of KCL-286 in male healthy volunteers to establish dosing to be used in the SCI patient population. METHODS: The design was a double blind, randomized, placebo-controlled dose escalation study in 2 parts: a single ascending dose adaptive design with a food interaction arm, and a multiple ascending dose design. RARß2 mRNA expression was evaluated in white blood cells. RESULTS: At the highest single and multiple ascending doses (100 mg), no trends or clinically important differences were noted in the incidence or intensity of adverse events (AEs), serious AEs or other safety assessments with none leading to withdrawal from the study. The AEs were dry skin, rash, skin exfoliation, raised liver enzymes and eye disorders. There was an increase in mean maximum observed concentration and area under the plasma concentration-time curve up to 24 h showing a trend to subproportionality with dose. RARß2 was upregulated by the investigational medicinal product in white blood cells. CONCLUSION: KCL-286 was well tolerated by healthy human participants following doses that exceeded potentially clinically relevant plasma exposures based on preclinical in vivo models. Target engagement shows the drug candidate activates its receptor. These findings support further development of KCL-286 as a novel oral treatment for SCI.

Reduced-sodium roasted chicken: Physical/technological characteristics, optimized KCl-seasoning mixture, consumer perception, liking, emotions, and purchase intent.

For thousands of years, sodium chloride (NaCl) has been used as a preservative and flavor enhancer. In the organism, NaCl plays a role in nerve functions, osmotic pressure, and nutrient absorption. However, high consumption of NaCl could lead to health issues, such as hypertension and heart-related problems. For these reasons, potassium chloride (KCl) has been considered a salt substitute in foods, but KCl could be limited to food matrixes because of its unwanted bitterness and metallic aftertaste. As a result, the objective of this study was to analyze KCl-reduced-sodium roasted chicken in physical/technological characteristics, KCl-seasoning mixture, consumer perception, liking, emotions, and purchase intent (PI). An extreme vertice mixture design decided granulated garlic (74.09%), black pepper (9.95%), smoked paprika (14.47%), and KCl (1.39%) ratio of good seasoning-KCl mixture for roasted chicken based on sensory attributes used on the desirability function methodology. After optimizing the KCl-seasoning blend, NaCl/KCl replacement levels (0%, 25%, 50%, 75%, and 100%) were established and evaluated consumer perception, liking, emotions, and PI. Adding 25% and 50% of KCl showed no significant (p > 0.05) impact on the sensory attributes. Likewise, PI significantly (p < 0.05) increased when utilizing 25% and 50% of KCl after panelists received information about sodium health risks (SHR). Regarding emotional responses, unsafe and worried significantly (p < 0.05) decreased among the highest KCl replacement levels (75% and 100%) after panelists obtained the SHR. Overall liking, gender, age, salt user, and positive emotional responses (satisfied and pleased) were decisive predictors concerning PI among panelists.