Gastrointestinal tolerability of organic infant formula compared to traditional infant formula: A systematic review

BACKGROUND Infants'nutrition significantly influences their growth,development,and overall well-being.With the increasing demand for organic infant formula driven by the perception of health benefits and growing awareness of natural feeding options,it is crucial to conduct a comparative analysis of the gastrointestinal tolerability between organic and traditional infant formulas.AIM To provide a concise and precise analysis of the gastrointestinal tolerability of organic infant formula compared to traditional infant formula.Due to limited direct comparisons,the review synthesizes available literature on each formula type,presenting insights into their potential effects on infants'digestive health.METHODS An extensive literature search was conducted,compiling studies on organic and traditional infant formulas,their compositions,and reported effects on gastrointestinal tolerability.We searched academic databases such as PubMed and Google Scholar and specialized nutrition,paediatrics,and infant health journals using relevant keywords till October 1,2023.RESULTS Although specific comparative studies are scarce and formula heterogeneity is a significant limitation,this systematic review provides an in-depth understanding of organic infant formulas'composition and potential benefits.While scientific evidence directly comparing gastrointestinal tolerability is limited,organic formulas strive to use carefully selected organic ingredients to imitate breast milk composition.Potential benefits include improved lipid profiles,higher methionine content,and decreased antibiotic-resistant bacteria levels.Understanding the gastrointestinal tolerability of organic and traditional infant formulas is crucial for parents and healthcare providers to make informed decisions.CONCLUSION Despite limitations in direct comparisons,this systematic review provides insights into the composition and potential benefits of organic infant formulas.It emphasizes the need for further research to elucidate their gastrointestinal effects comprehensively.

Safety, Tolerability and Anti-Diarrhoeal Activity of “Diarra”, a Preparation of Medicinal Plants Used in Ivorian Traditional Medicine

Background: “Diarra”, a traditional herbal remedy made from five (5) medicinal plants, might be endowed with anti-diarrhoeal properties according to its owner. However, scientific evidence of its safety, tolerability and activity has not been established. Objective: This study aimed to assess the safety, tolerability and anti-diarrhoeal activity of “Diarra” in experimental rats. Materials and Methods: Safety was assessed by acute (OECD 423) and sub-acute (OECD 407) toxicity studies at doses of 5, 10 and 20 mg/kg. Clinical tolerability was assessed for 28 days. On day 29, a blood sample was taken to evaluate biological tolerability. The anti-diarrhoeal activity was investigated in a castor oil-induced diarrhoea model. Rats were given the remedy at doses of 5, 10 and 20 mg/kg and then castor oil 1 hour later. They were observed for 4 hours and diarrhoeal stools were collected. The Percentage of diarrhoeal inhibition was calculated. Results: A single dose of “Diarra” at a dose of 2000 mg/kg did not induce any lethality, behavioural or weight change in rats for 14 days. When administered once daily for 28 days, “Diarra” did not cause lethality or significant behavioural disorders or significant weight loss in rats. No biological disorders were observed. The treatment of rats with “Diarra” at doses of 5 mg/kg, 10 mg/kg and 20 mg/kg in a single administration inhibited the occurrence of diarrhoeal stools. The respective percentages of inhibition were 60%, 50% and 62%, similar to those of loperamide at a dose of 2 mg/kg (68%). Conclusion: “Diarra” has an anti-diarrheal activity in rats. It is also safe to use this remedy as such.

Safety,Tolerability and Pharmacokinetic Study of Recombinant Human Parathyroid Hormone [rhPTH(1-84)] in Chinese Healthy Volunteers

The current study was designed to determine the safety, tolerability and pharmacokinetic parameters of recombinant human parathyroid hormone [rhPTH （1-84）] used for the treatment of osteoporosis. In the single-dose format pharmacokinetic study, thirty-six healthy male volunteers received three dose levels of rhPTH （1-84） subcutaneously： 1, 2, and 4 μg/kg. The blood was timing drawn and the serum concentration of rhPTH （1-84） was determined by enzyme linked immunosorbent assay （ELISA）. Serum concentration-time curves of PTH （1-84） exhibited a double-peak pattern, the first peak appearing about 10 to 30 min after administration and the second peak occurring about 1.5 to2 h after administration. Serum terminal half-time of PTH （1-84） was approximately 2 h. The parameters indicated the serum levels were directly proportional to the administered dose, with the mean Cmax and AUC0_24 ranging from approximately 543.47 to 1845 pg/mL and 2358.6 to 9232.12 pg.h.mL^-1 over the dose range. The drug was well tolerated, the clinical symptoms were generally mild and of short duration.

Efficacy and tolerability of high and low-volume bowel preparation compared:A real-life single-blinded large-population study

BACKGROUND Low-volume preparations for colonoscopy have shown similar efficacy compared to high-volume ones in randomized controlled trials(RCT).However,most RCTs do not provide data about clinical outcomes including lesions detection rate.Moreover,real-life comparisons are lacking.AIM To compare efficacy(both in terms of adequate bowel preparation and detection of colorectal lesions)and tolerability of a high-volume(HV:4 L polyethylene glycol,PEG)and a low-volume(LV:2 L PEG plus bisacodyl)bowel preparation in a real-life setting.METHODS Consecutive outpatients referred for colonoscopy were prospectively enrolled between 1 December 2014 and 31 December 2016.Patients could choose either LV or HV preparation,with a day-before schedule for morning colonoscopies and a split-dose for afternoon procedures.Adequate bowel preparation according to Boston Bowel Preparation Scale(BBPS),clinical outcomes including polyp detection rate(PDR),adenoma detection rate(ADR),advanced adenoma detection rate(AADR),sessile/serrated lesion detection rate(SDR)and cancer detection rate and self-reported tolerability of HV and LV were blindly assessed.RESULTS Total 2040 patients were enrolled and 1815(mean age 60.6 years,50.2%men)finally included.LV was chosen by 52%of patients(50.8%of men,54.9%of women).Split-dose schedule was more common with HV(44.7%vs 38.2%,P=0.005).High-definition scopes were used in 33.4%of patients,without difference in the two groups(P=0.605).HV and LV preparations showed similar adequate bowel preparation rates(89.2%vs 86.6%,P=0.098),also considering the two different schedules(HV split-dose 93.8%vs LV split-dose 93.6%,P=1;HV daybefore 85.5%vs LV day-before 82.3%,P=0.182).Mean global BBPS score was higher for HV preparations(7.1±1.7 vs 6.8±1.6,P<0.001).After adjustment for sex,age and indications for colonoscopy,HV preparation resulted higher in PDR[Odds ratio(OR)1.32,95%CI:1.07-1.63,P=0.011]and ADR(OR 1.29,95%CI 1.02–1.63,P=0.038)and comparable to LV in AADR(OR 1.51,95%CI 0.97-2.35,P=0.069),SDR and cancer detection rate.The use of standard-definition colonoscopes was associated to lower PDR(adjusted OR 1.59,95%CI:1.22-2.08,P<0.001),ADR(adjusted OR 1.71,95%CI:1.26–2.30,P<0.001)and AADR(adjusted OR 1.97,95%CI:1.09-3.56,P=0.025)in patients receiving LV preparation.Mean Visual Analogue Scale tolerability scored equally(7,P=0.627)but a≥75%dose intake was more frequent with LV(94.6%vs 92.1%,P=0.003).CONCLUSION In a real-life setting,PEG-based low-volume preparation with bisacodyl showed similar efficacy and tolerability compared to standard HV preparation.However,with higher PDR and ADR,HV should still be considered as the reference standard for clinical trials and the preferred option in screening colonoscopy,especially when colonoscopy is performed with standard resolution imaging.

Pharmacokinetics and Tolerability of Oral Dosage Forms of Huperzine A in Healthy Chinese Male Volunteers: a Randomized,Single Dose, Three-period, Six-sequence Crossover Study

Huperzine A is a potent, reversible, and blood-brain barrier permeable acetylcholinesterase inhibitor. The aim of this study was to compare the pharmacokinetics, tolerability, and bioavailability of two formulations with the established reference formulation of huperzine A in a fasting, healthy Chinese male population. This was a randomized, single-dose, 3-period, 6-sequence crossover study. The plasma concentrations of huperzine A were determined by liquid chromatography tandem mass spectrometry. Tolerability was assessed based on subject interview, vital sign monitoring, physical examination, and routine blood and urine tests. The mean（SD） pharmacokinetic parameters of the reference drug were Cmax, 1.550（0.528） ng/m L; t1/2, 12.092（1.898） h; AUC0-72 h, 17.550（3.794） ng·h/m L. Those of the test formulation A and test formulation B were Cmax, 1.412（0.467）, 1.521（0.608） ng/m L; t1/2, 12.073（2.068）, 12.271（1.678） h; AUC0-72 h, 15.286（3.434） ng·h/mL, 15.673（3.586） ng·h/m L. The 90% confidence intervals for the AUC0-72 h and Cmax were between 0.80 and 1.25. No adverse events were reported by the subjects or found with results of clinical laboratory test. The test and reference products met the regulatory criteria for bioequivalence in these fasting, healthy Chinese male volunteers. All three formulations appeared to be well tolerated.

Prospective single-blinded single-center randomized controlled trial of Prep Kit-C and Moviprep:Does underlying inflammatory bowel disease impact tolerability and efficacy?

BACKGROUND Colonoscopy remains the gold standard for detection of colonic disease.An optimal evaluation depends on adequate bowel cleansing.Patients with inflammatory bowel disease(IBD),require frequent endoscopic assessment for both activity and dysplasia assessment.Two commonly used bowel preparations in Australia are Prep Kit-C(Pc)and Moviprep(Mp).Little is known about tolerability,efficacy and safety of split protocols of Mp and Pc in both IBD and non-IBD patients.AIM To primary aim was to compare the tolerability,efficacy and safety of split protocols of Mp and Pc in patients having a colonoscopy.The secondary aim was to compare the efficacy,tolerability and safety of either preparation in patients with or without IBD.METHODS Patients were randomized to Pc or Mp bowel preparation.Patients completed a questionnaire to assess tolerability.Efficacy was assessed using the Ottawa Bowel Preparation Score.Serum electrolytes and renal function were collected one week prior to colonoscopy and on the day of colonoscopy.RESULTS Of 338 patients met the inclusion criteria.Of 168 patients randomized to Mp and 170 to Pc.The efficacy of bowel preparation(mean Ottawa Bowel Preparation Score)was similar between Mp(5.4±2.4)and Pc(5.1±2.1)(P=0.3).Mean tolerability scores were similar in Mp(11.84±5.4)and Pc(10.99±5.2;P=0.17).125 patients had IBD(73 had Crohn’s Disease and 52 had Ulcerative colitis).Sixtyfour IBD patients were allocated to Mp and 61 to Pc.In non-IBD patients,104 were allocated to Mp and 109 to Pc.The mean tolerability score in the IBD group was lower than the non-IBD group(mean tolerability scores:IBD:10.3±5.1 and non-IBD:12.0±5.3;P=0.01).IBD patients described more abdominal pain with Mp when compared with Pc;(Mp:5.7±4.4 vs Pc:3.6±2.6,P=0.046).Serum magnesium level increased with Pc compared with Mp in all patients(mean increase in mmol/L:Mp:0.03±0.117 and Pc:0.11±0.106;P<0.0001).CONCLUSION In this study,the efficacy,tolerability and safety of Mp and Pc were similar in all patients.However,patients with IBD reported lower tolerability with both preparations.Specifically,IBD patients had more abdominal pain with Mp.These results should be considered when recommending bowel preparation especially to IBD patients.

Clinical benefit and tolerability of adjuvant intraperitoneal chemotherapy in patients who have or have not received neoadjuvant chemotherapy for advanced ovarian cancer

BACKGROUND Adjuvant chemotherapy using intraperitoneal(IP)treatment has demonstrated survival benefit over intravenous(IV)therapy alone in patients treated with upfront debulking surgery for advanced stage ovarian cancer.Neoadjuvant chemotherapy followed by interim surgery and adjuvant chemotherapy has similar outcome in survival as compared to upfront surgery followed by adjuvant IV chemotherapy.IP chemotherapy has not been widely adopted in clinical practice for a number of reasons.Whether IP chemotherapy delivered in the patients who received neoadjuvant chemotherapy can be well tolerated or confers any clinical benefit has not been well studied.AIM To evaluate the experience of adjuvant IP chemotherapy in the community cancer clinic setting,and the clinical benefit and tolerability of incorporating IP chemotherapy in patients who received neoadjuvant treatment.METHODS We retrospectively evaluated toxicities and outcomes of patients with stage III and IV ovarian cancer diagnosed at our institution between 07/2007 and 07/2015 who received intraperitoneal chemotherapy after cytoreductive surgery(group 1)or after neoadjuvant chemotherapy followed by interim surgery(group 2).RESULTS Thirty eight patients were treated with IP chemotherapy,median age was 54 years old(range 38.6 to 71 years).In group 1(n=25),12(48%)of the patients completed 4 or more cycle of IP treatment after upfront debulking surgery;while in group 2(n=13),8(61.5%)of the patients completed all 3 cycles of the assigned IP chemotherapy after receiving neoadjuvant IV chemotherapy followed by surgery,and 2(15.4%)more patients tolerated more than 3 cycles.In those patients who did not get planned IP chemotherapy,most of them were treated with substitutional IV chemotherapy,and the completion rate for 6 cycles of IV+IP was 92%.Abdominal pain,(64%in group 1 and 38%in group 2),vomiting,(36%in group 1 and 30.8%in group 2),dehydration(16%in group 1 and 15.4%in group 2),and hypomagnesemia(12%in group 1 and 15.4%in group 2)were the most common adverse effects in all patients,while patients who have received neoadjuvant chemotherapy were more likely to get hypokalemia,fatigue and renal insufficiency.Progression free survival(PFS)was 26.5 mo(95%CI 14.9,38.0)in group 1 and 27.6 mo(95%CI 13.1,42.1)in group 2.The overall survival was 100.2 mo(95%CI 67.9,132.5)for group 1 and 68.2 mo(95%CI 32.2,104.0)for group 2.For the entire cohort,PFS was 26.5 mo(95%CI 15.9,37.0)and OS was 78.8 mo(95%CI 52.3,105.4).CONCLUSION The use of IP/IV chemotherapy can be safely administrated in the community cancer clinic setting.The use of IP/IV chemotherapy in patients who have received neoadjuvant chemotherapy followed by surgery is feasible and tolerable.Despite various modification of the IP regimen,incorporation of IP chemotherapy in the adjuvant setting appears to be associated with improved PFS and overall survival.

Efficacy and tolerability of hydrogen carbonate-rich waterfor heartburn

AIM To investigate the efficacy and safety of mineralwater with a high content of hydrogen carbonate inpatients with heartburn.METHODS： This open, single-center, single-armclinical pilot study enrolled 50 patients, 18-64 yearsold, who had been suffering from heartburn at leasttwice a week for at least 3 mo before entering thestudy. Pharmacological treatment of heartburn was notpermitted, and patients with severe organic diseaseswere excluded. After a run-in period of one week, theparticipants received 1.5 L of the test water for thefollowing 6 wk; 300 mL with meals t.i.d., the remainderto be drunk throughout the day. During the trial, therewere five visits at the study center （screening, baseline,two interim visits and the final visit）. The efficacyendpoints included incidence and duration of heartburnepisodes per week by patient＇s self-assessment （heartburndiary） as well as changes in symptom severity asper symptom specific questionnaires [Reflux Disease Questionnaire （RDQ）; Quality of Life in Reflux andDyspepsia （QOLRAD）; Gastrointestinal Quality of LifeIndex] and overall health-related quality of life per SF-12（12-question short form） at each visit. At the end of thestudy, patients and investigators independently ratedthe overall efficacy of the test water on a 4-point Likertscale. Safety was assessed by evaluation of adverseevents （AEs）, vital signs （heart rate, blood pressure）and laboratory parameters. Changes from initial to finalexaminations were assessed by the non-parametricWilcoxon test; categorical variables were comparedusing the χ 2 test, and for more than 5 categories, by theU-test.RESULTS： Twenty-eight participants were men, 22women. The mean age of the patients in the fullanalysis set/intention-to treat population （FAS/ITT） was40.6 years. Forty-two participants completed the studyaccording to the study protocol and formed the perprotocolset （PP population）; 48 participants drank thewater at least once as requested and were analyzedas ITT population. The occurrence of heartburn wasstatistically significantly reduced at wk 6 in both the ITTand the PP populations. At wk 6, the mean number ofheartburn episodes/week decreased by 5.1 episodes（P 〈 0.001） and the mean duration of heartburnsymptoms by 19 min （ITT） （P = 0.002）. The frequencyof heartburn symptoms was reduced in 89.6% of thepatients （P 〈 0.001）, and the duration of symptoms in79.2% of patients （ITT） （P 〈 0.001）. All dimensions ofthe RDQ （heartburn, regurgitation, gastro-esophagealreflux disease symptoms, dyspepsia） showed asignificant improvement at 6 wk. Likewise, diseasespecificquality of life improved significantly （QOLRAD,GIQLI）. Overall, 89.4% of patients rated the efficacyof the test water as ＂good＂ or ＂very good＂, as did theinvestigators for 91.5% of the patients. There wereno serious AEs. After 6 wk, systolic and diastolic bloodpressure values decreased slightly but significantly [-3.5and -3.0 mmHg, respectively （P = 0.008 and P = 0,002）].Ninety-six percent of patients and investigators for thesame percentage of patients rated the tolerability of thewater as ＂good＂ or ＂very good＂.CONCLUSION： The data demonstrate effectiveness ofa hydrogen carbonate-rich mineral water in alleviatingheartburn frequency and severity, thereby improvingquality of life. The water has excellent tolerability.

Tolerability of a Proprietary Larch Arabinogalactan Extract: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial in Healthy Subjects

In a placebo-controlled, double-blind, randomized clinical trial, the tolerability of a proprietary larch arabinogalactan preparation (ResistAidTM) was investigated. METHODS: 199 healthy participants were randomly assigned to receive either placebo (n = 98) or an arabinogalactan preparation (n = 101) over a period of 12 weeks. As safety parameters the total number of adverse events, changes in various biochemical and laboratory parameters as well as the global evaluation of tolerability by investigator and subjects compared to placebo were evaluated. RESULTS: In total 16 adverse events were observed in 16 subjects, with no difference between the arabinogalactan and the placebo group (p = 0.935). There were no differences in the mean changes of the measured biochemical and laboratory parameters. The tolerability of the arabinogalactan extract was rated as “very good” or “good” by the investigators for 99% of the subjects and by 98% subjects in self-assessment with no statistical differences to placebo. CONCLUSION: The measured parameters as well as the evaluation of the tolerability by the investigators and the subjects demonstrate a very good tolerance profile of the proprietary arabinogalactan extract with no differences to placebo when taken for 12 weeks.

Safety and Tolerability of Edivoxetine for Long-Term Treatment of Major Depressive Disorder in Adult Patients

This 12-month open-label, but dose-blinded extension phase, evaluated the safety and tolerability of flexibly-dosed edivoxetine (6, 9, 12 or 18 mg once daily) in patients (N = 397) with major depressive disorder, who completed the 10-week randomized, double-blind, placebo-controlled acute phase of the study.All patients were treated with edivoxetine during the extension phase. The mean age of the patients was 45 years, and most were white females. Safety evaluations included assessment of treatment-emergent adverse events (TEAEs), laboratory and vital sign measures, and suicidality. Within-group t-tests based on a 2-sided significance level of 0.05 and 95% confidence levels were used to assess whether changes from baseline were statistically significant from zero. The overall completion rate was 54%. Adverse event was the most common (14.4%) reason for discontinuation, which included blood pressure increased (1.3%), heart rate increased (1.3%), anxiety (1.0%), and tachycardia (1.0%). At least 1 TEAE was reported by 72.3% of patients, of which headache (10.8%) and hyperhidrosis (10.1%) were the most common;2.8% of patients had ≥1 serious adverse events, and there were no completed suicides. No clinically relevant changes were observed in most laboratory measures. Potentially clinically significant changes in ALT values occurred in 1.8% of patients, and either normalized or had decreased by the last assessment. Mean increases in blood pressure and pulse were consistent with those observed in the acute phase and appeared to reach a plateau within 3 to 5 months of treatment. In conclusion, safety and tolerability findings during this long-term extension phase evaluation of edivoxetine were consistent with its norepinephrine reuptake inhibition profile.

Safety and Tolerability of Transdermal Rotigotine in a Clinical Practice Cohort for 2 Years

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disease that occurs as a result of loss of dopaminergic neurons from the substantia nigra. Rotigotine is a non-ergolinic dopamine agonist available as a silicone-based transdermal patch for the treatment of PD. In the European Union, rotigotine transdermal patch is indicated for use as monotherapy in early idiopathic PD, or in combination with levodopa through the disease course to the late stages where motor complications with levodopa become an issue. Objective: To investigate the safety and tolerability of transdermal rotigotine, in patients with PD being treated during routine clinical practice for 2 years. Results: 114 patients were enrolled, and evaluated for adverse events over a 24-month period. Adverse events occurred in 39 patients (34.21%). 23 patients (20.17%) reported application site reactions (dermatitis, erythema, itching), and 16 (14.03%) had systemic adverse events. Sleep disorders were the most common problem;the others were hallucinations, depression, dizziness, and syncope. No patient experienced dyskinesia. Adverse events necessitated the discontinuation of rotigotine for application site reactions in fourteen patients (12.28%) and 11 patients (9.64%);reasons for discontinuation were systemic adverse events. Conclusion: Rotigotine is safe and well tolerated when used to treat PD in routine clinical practice.

On tolerability and safety of a maintenance treatment with 6-thioguanine in azathioprineor 6-mercaptopurine intolerant IBD patients

AIM: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 year.METHODS: Database analysis.RESULTS: Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8×108 RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%)and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had splenomegaly.CONCLUSION: The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials.

An Environment‑Tolerant Ion‑Conducting Double‑Network Composite Hydrogel for High‑Performance Flexible Electronic Devices

High-performance ion-conducting hydrogels(ICHs)are vital for developing flexible electronic devices.However,the robustness and ion-conducting behavior of ICHs deteriorate at extreme tempera-tures,hampering their use in soft electronics.To resolve these issues,a method involving freeze–thawing and ionizing radiation technology is reported herein for synthesizing a novel double-network(DN)ICH based on a poly(ionic liquid)/MXene/poly(vinyl alcohol)(PMP DN ICH)system.The well-designed ICH exhibits outstanding ionic conductivity(63.89 mS cm^(-1) at 25℃),excellent temperature resistance(-60–80℃),prolonged stability(30 d at ambient temperature),high oxidation resist-ance,remarkable antibacterial activity,decent mechanical performance,and adhesion.Additionally,the ICH performs effectively in a flexible wireless strain sensor,thermal sensor,all-solid-state supercapacitor,and single-electrode triboelectric nanogenerator,thereby highlighting its viability in constructing soft electronic devices.The highly integrated gel structure endows these flexible electronic devices with stable,reliable signal output performance.In particular,the all-solid-state supercapacitor containing the PMP DN ICH electrolyte exhibits a high areal specific capacitance of 253.38 mF cm^(-2)(current density,1 mA cm^(-2))and excellent environmental adaptability.This study paves the way for the design and fabrication of high-performance mul-tifunctional/flexible ICHs for wearable sensing,energy-storage,and energy-harvesting applications.

MIR1868 negatively regulates rice cold tolerance at both the seedling and booting stages

Low temperature causes rice yield losses of up to 30%–40%,therefore increasing its cold tolerance is a breeding target.Few genes in rice are reported to confer cold tolerance at both the vegetative and reproductive stages.This study revealed a rice-specific 24-nt miRNA,miR1868,whose accumulation was suppressed by cold stress.Knockdown of MIR1868 increased seedling survival,pollen fertility,seed setting,and grain yield under cold stress,whereas its overexpression conferred the opposite phenotype.Knockdown of MIR1868 increased reactive oxygen species(ROS)scavenging and soluble sugar content under cold stress by increasing the expression of peroxidase genes and sugar metabolism genes,and its overexpression produced the opposite effect.Thus,MIR1868 negatively regulated rice cold tolerance via ROS scavenging and sugar accumulation.

Compositional and Hollow Engineering of Silicon Carbide/Carbon Microspheres as High-Performance Microwave Absorbing Materials with Good Environmental Tolerance

Microwave absorbing materials(MAMs)characterized by high absorption efficiency and good environmental tolerance are highly desirable in practical applications.Both silicon carbide and carbon are considered as stable MAMs under some rigorous conditions,while their composites still fail to produce satisfactory microwave absorption performance regardless of the improvements as compared with the individuals.Herein,we have successfully implemented compositional and structural engineering to fabricate hollow Si C/C microspheres with controllable composition.The simultaneous modulation on dielectric properties and impedance matching can be easily achieved as the change in the composition of these composites.The formation of hollow structure not only favors lightweight feature,but also generates considerable contribution to microwave attenuation capacity.With the synergistic effect of composition and structure,the optimized SiC/C composite exhibits excellent performance,whose the strongest reflection loss intensity and broadest effective absorption reach-60.8 dB and 5.1 GHz,respectively,and its microwave absorption properties are actually superior to those of most SiC/C composites in previous studies.In addition,the stability tests of microwave absorption capacity after exposure to harsh conditions and Radar Cross Section simulation data demonstrate that hollow SiC/C microspheres from compositional and structural optimization have a bright prospect in practical applications.

Abiotic stress treatment reveals expansin like A gene OfEXLA1 improving salt and drought tolerance of Osmanthus fragrans by responding to abscisic acid

Sweet osmanthus(Osmanthus fragrans) is a having general approval aromatic tree in China that is widely applied to landscaping and gardening. However, the evergreen tree adaptability is limited by many environmental stresses. Currently, limited information is available regarding the genetic analysis and functional identification of expansin genes in response to abiotic stress in sweet osmanthus. In this study, a total of 29 expansin genes were identified and divided into four groups by genome-wide analysis from the sweet osmanthus genome. Transcriptome and quantitative Real-time PCR analysis showed that the cell wall-localized protein expansin-like A(OfEXLA1) gene was significantly induced by salt and drought treatment. Histochemical GUS staining of transgenic Arabidopsis lines in which GUS activity was driven with the OfEXLA1 promoter, GUS activity was significantly induced by salt, drought, and exogenous abscisic acid(ABA). In yeast, we found OfEXLA1overexpression significantly improved the population of cells compared with wild-type strains after NaCl and polyethylene glycol(PEG)treatment. Additionally, OfEXLA1 overexpression not only promoted plant growth, but also improved the salt and drought tolerance in Arabidopsis. To gain insight into the role of ABA signaling in the regulation of OfEXLA1 improving abiotic tolerance in sweet osmanthus, four differentially expressed ABA Insensitive 5(ABI5)-like genes(OfABL4, OfABL5, OfABL7, and OfABL8) were identified from transcriptome, and dualluciferase(dual-LUC) and yeast one hybrid(Y1H) assay showed that OfABL4 and OfABL5 might bind to OfEXLA1 promoter to accumulate the OfEXLA1 expression by responding to ABA signaling to improve abiotic tolerance in sweet osmanthus. These results provide the information for understanding the molecular functions of expansin-like A gene and molecular breeding of sweet osmanthus in future.

Safety and tolerability of the ketogenic diet used for the treatment of refractory childhood epilepsy: a systematic review of published prospective studies

Background:To review the available evidence from prospective studies on the safety and tolerability of the ketogenic diet (KD) for the treatment of refractory childhood epilepsy.Methods:A comprehensive bibliographic search was performed with the aim of retrieving prospective studies that monitored adverse effects (AEs) in children after receiving the classic or medium-chain triglyceride KD therapy for refractory epilepsy.Results:A total of 45 studies were retrieved,including 7 randomized controlled trials.More than 40 categories of AEs were reported.The most common AEs included gastrointestinal disturbances (40.6%),hyperlipidemia (12.8%),hyperuricemia (4.4%),lethargy (4.1%),infectious diseases (3.8%) and hypoproteinemia (3.8%).Severe AEs,such as respiratory failure and pancreatitis,occurred in no more than 0.5% of children.Specifically,patients receiving KD therapy should be monitored for osteopenia,urological stones,right ventricular diastolic dysfunction,and growth disturbance.The total retention rates of the diet for 1 year and 2 years were 45.7% and 29.2%,respectively.Nearly half of the patients discontinued the diet because of lack of efficacy.AEs were not the main reason for the KD discontinuation.None of the 24 deaths reported after initiation of the diet was attributed to the KD.Conclusions:KD is a relatively safe dietary therapy.However,because the KD can cause various AEs,it should be implemented under careful medical supervision.Continuous follow-up is needed to address the long-term impact of the diet on the overall health of children.

A Data Intrusion Tolerance Model Based on an Improved Evolutionary Game Theory for the Energy Internet

Malicious attacks against data are unavoidable in the interconnected,open and shared Energy Internet(EI),Intrusion tolerant techniques are critical to the data security of EI.Existing intrusion tolerant techniques suffered from problems such as low adaptability,policy lag,and difficulty in determining the degree of tolerance.To address these issues,we propose a novel adaptive intrusion tolerance model based on game theory that enjoys two-fold ideas:(1)it constructs an improved replica of the intrusion tolerance model of the dynamic equation evolution game to induce incentive weights;and (2)it combines a tournament competition model with incentive weights to obtain optimal strategies for each stage of the game process.Extensive experiments are conducted in the IEEE 39-bus system,whose results demonstrate the feasibility of the incentive weights,confirm the proposed strategy strengthens the system’s ability to tolerate aggression,and improves the dynamic adaptability and response efficiency of the aggression-tolerant system in the case of limited resources.

Boosting oxygen reduction activity and CO_(2) resistance on bismuth ferrite-based perovskite cathode for low-temperature solid oxide fuel cells below 600℃

Developing efficient and stable cathodes for low-temperature solid oxide fuel cells(LT-SOFCs) is of great importance for the practical commercialization.Herein,we propose a series of Sm-modified Bi_(0.7-x)Sm_xSr_(0.3)FeO_(3-δ) perovskites as highly-active catalysts for LT-SOFCs.Sm doping can significantly enhance the electrocata lytic activity and chemical stability of cathode.At 600℃,Bi_(0.675)Sm_(0.025)Sr_(0.3)FeO_(3-δ)(BSSF25) cathode has been found to be the optimum composition with a polarization resistance of 0.098 Ω cm^2,which is only around 22.8% of Bi_(0.7)Sr_(0.3)FeO_(3-δ)(BSF).A full cell utilizing BSSF25 displays an exceptional output density of 790 mW cm^(-2),which can operate continuously over100 h without obvious degradation.The remarkable electrochemical performance observed can be attributed to the improved O_(2) transport kinetics,superior surface oxygen adsorption capacity,as well as O_(2)p band centers in close proximity to the Fermi level.Moreover,larger average bonding energy(ABE) and the presence of highly acidic Bi,Sm,and Fe ions restrict the adsorption of CO_(2) on the cathode surface,resulting in excellent CO_(2) resistivity.This work provides valuable guidance for systematic design of efficient and durable catalysts for LT-SOFCs.

Gastric cancer liver metastasis will reduce the efficacy of immunotherapy

Immune checkpoint inhibitors augment the antitumor activity of T cells by inhibiting the negative regulatory pathway of T cells,leading to notable efficacy in patients with non-small cell lung cancer,melanoma,and other malignancies through immunotherapy utilization.However,secondary malignant liver tumors not only lower the liver's sensitivity to immunotherapy but also trigger systemic immune suppression,resulting in reduced overall effectiveness of immune therapy.Patients receiving immunotherapy for non-small cell lung cancer and melanoma experience reduced response rates,progression-free survival,and overall survival when secondary malignant tumors develop in the liver.Through Liu's retrospective analysis,valuable insights are provided for the future clinical management of these patients.Therefore,in patients with gastric cancer(GC),the occurrence of liver metastasis might be indicative of reduced efficacy of immuno-therapy.Overcoming liver immune tolerance mechanisms and their negative impacts allows for the potential benefits of immunotherapy in patients with GC and liver metastasis.INTRODUCTION Gastric cancer(GC)ranks among the prevalent malignancies affecting the digestive system globally.Based on the latest epidemiological data[1,2],it holds the fifth position for incidence and the fourth position for mortality among all malignant tumors.GC cases and fatalities in China make up roughly half of the worldwide figures.Earlier investigations[3]have demonstrated that the median overall survival(mOS)among advanced GC patients left untreated typically ranges from 3 to 4 months.Systemic chemotherapy recipients often experience a mOS of around one year,accompanied by a marked improvement in the quality of life among patients with advanced GC.The mainstay of treatment for advanced GC patients involves chemotherapeutic medications such as fluoropyrimidines,platinum compounds,and taxanes.However,their efficacy in tumor control is constrained by acquired resistance and primary resistance.The rise of personalized precision therapy has propelled immunotherapy into the spotlight as a crucial component of comprehensive treatment[4].By blocking the negative regulatory pathways of T cells,immune checkpoint inhibitors(ICIs)boost the anti-tumor effect of T cells.Immunotherapy has brought about significant therapeutic benefits for patients diagnosed with non-small cell lung cancer,melanoma,and related illnesses[5,6],instilling newfound hope in those with advanced GC[7].However,phase III clinical trial data[8-12]reveals that the incorporation of immunotherapy into chemotherapy regimens improves overall survival(OS)outcomes for patients with advanced GC.The liver's immune-exempt nature renders it less responsive to immunotherapy when secondary malignant tumors are present,fostering systemic immune suppression and yielding unfavorable outcomes in immune therapy[13-15].In retrospective research[16-20]pertaining to non-small cell lung cancer and melanoma,it has been observed that the presence of secondary liver malignancies may lower the response rate,progression-free survival(PFS),and OS rates in patients treated with immunotherapy,independent of factors such as tumor mutation burden and PD-L1 expression.Despite this,there is a paucity of studies examining whether the existence of secondary malignant liver tumors affects the effectiveness of immunotherapy in patients diagnosed with advanced HER-2 negative GC.