Coaching Pediatricians for Wellbeing: A Pilot Feasibility and Acceptability Study.

OBJECTIVE: Organization-sponsored interventions have the potential to promote, and destigmatize seeking help for, wellbeing. Our study objective was to explore the acceptability and feasibility of a coaching intervention to improve wellbeing among faculty. METHODS: We conducted a pilot, pre/post design, study in a convenience sample of pediatric faculty at an academic medical center. Participants were offered <6 live virtual coaching sessions at the participant's discretion. In addition, a novel wellbeing individual development plan (WB-IDP) was distributed to participants. Primary outcomes were feasibility of the intervention, defined as completing >1 coaching session and acceptability measured by anonymous feedback and use of the WB-IDP. Secondary outcomes were wellbeing (WHO Wellbeing Index (WHO-5)), stress (Perceived Stress Scale (PSS)), and work engagement (Utrecht Work Engagement Scale (UWES)), at baseline, 3, and 6 months. RESULTS: All enrollees (N=28) completed at least one, 18/28 (64%) completed at least 4, and 9/28 (32%) completed 6 coaching sessions. Of 28 participants, 11 (39%) started a WB-IDP and 5/28 (18%) completed and implemented the plan. The aggregate WHO-5 score showed a statistically significant change from baseline (53.3) to month 6 (64.3) (P <.01). Fourteen 14/27 (52%) participants had an improvement of ≥10 points in WHO-5 score between baseline and month 6. No other significant changes were observed. CONCLUSION: Individualized certified coaching for wellbeing was successfully implemented and associated with a significant increase in wellbeing. We speculate that wellbeing coaching can be promoted by faculty development programs in university and healthcare settings and has potential to improve organizational outcomes.

Plantar massage or ankle mobilization do not alter gait biomechanics in those with chronic ankle instability: a randomized controlled trial.

OBJECTIVES: Chronic ankle instability (CAI) is characterized by persistent neuromechanical impairments following an initial lateral ankle sprain. Ankle joint mobilization and plantar massage have improved the range of motion and static postural control in those with CAI. This study aimed to determine the impact of two-week joint mobilization and plantar massage interventions on gait kinematics and kinetics in individuals with CAI. METHODS: A single-blind randomized trial was conducted with 60 participants with CAI, randomized into three groups: joint mobilization (n = 20), plantar massage (n = 20), and control (n = 20). The two treatment groups received six 5-min sessions manual therapy over a 2-week, while the control group received no intervention. Gait biomechanics were assessed on an instrumented treadmill before and after the intervention using 3D kinematics and kinetics analysis. Analyses compared biomechanical outcomes from each treatment group to the control group individually using a 1-dimensional statistical parametric mapping. The alpha level was set at p < 0.05. RESULTS: Eighteen participants per group were part of the final analysis. No significant main or interactions effects were found for ankle sagittal or frontal plane positions following either intervention (p > 0.05 for all comparisons). COP location relative to the lateral border of the foot also did not change (p > 0.05). CONCLUSION: The findings suggest that two-week joint mobilization and plantar massage interventions do not significantly alter gait biomechanics in individuals with CAI. These results support the need for gait-specific interventions to modify biomechanics in this population.

Community-engaged implementation of a safety bundle for pregnancy-related severe hypertension in the outpatient setting: protocol for a type 3 hybrid study with a multiple baseline design.

BACKGROUND: Hypertensive disorders of pregnancy are among the leading causes of maternal mortality and morbidity in the U.S., with rates highest among birthing people who are Black, rural residents, and/or have low-income. Severe hypertension, in particular, increases risk of stroke and other serious pregnancy complications. To promote early detection and treatment of severe hypertension, the Alliance for Innovation on Maternal Health developed the Severe Hypertension During Pregnancy and Postpartum Period Safety Bundle (HTN Bundle). Multiple studies have demonstrated the HTN Bundle's effectiveness in the inpatient setting. With funding from the National Heart, Lung, and Blood Institute, we engaged community partners to adapt the HTN Bundle for the outpatient setting (i.e., O-HTN Bundle) and planned for its implementation. In this paper, we describe the protocol for a study evaluating O-HTN Bundle implementation in 20 outpatient clinics serving Black, rural, and/or low-income populations. METHODS: This study is a hybrid type 3 effectiveness-implementation trial with a multiple baseline design. We will implement the O-HTN Bundle in three successive cohorts of clinics using a multicomponent implementation strategy to engage community partners (coalition, patient workgroup) and support clinics (training, facilitation, education materials, and simulations of severe hypertension events). To test the strategy, we will compare clinic fidelity to evidence-based guidelines for (a) patient education on hypertension and (b) blood pressure measurement technique, with repeated measures occurring before and after strategy receipt. We will also observe strategy effects on community- and clinic-level intermediate outcomes (community engagement, organizational readiness), implementation outcomes (reach, adoption, fidelity, maintenance), and effectiveness outcomes (receipt of guideline concordant care). Analyses will address whether outcomes are equitable across Black, rural, and/or low-income subgroups. Guided by the Consolidated Framework for Implementation Research 2.0, we will use mixed methods to identify adaptations and other determinants of implementation success. DISCUSSION: This study integrates community engagement and implementation science to promote equitable and timely response to severe HTN in the outpatient setting during pregnancy and postpartum. This is one of the first studies to implement an outpatient HTN Bundle and to use simulation as a strategy to reinforce team-based delivery of guideline concordant care. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov as "Testing Implementation Strategies to Support Clinic Fidelity to an Outpatient Hypertension Bundle (AC3HIEVE)." Registration number NCT06002165, August 21, 2023: https://clinicaltrials.gov/study/NCT06002165 .

Recent advances in DNAzymes for bioimaging, biosensing and cancer therapy.

DNAzymes, a class of single-stranded catalytic DNA with good stability, high catalytic activity, and easy synthesis, functionalization and modification properties, have garnered significant interest in the realm of biosensing and bioimaging. Their integration with fluorescent dyes or chemiluminescent moieties has led to remarkable bioimaging outcomes, while DNAzyme-based biosensors have demonstrated robust sensitivity and selectivity in detecting metal ions, nucleic acids, proteins, enzyme activities, exosomes, bacteria and microorganisms. In addition, by delivering DNAzymes into tumor cells, the mRNA therein can be cleaved to regulate the expression of corresponding proteins, which has further propelled the application of DNAzymes in cancer gene therapy and synergistic therapy. This paper reviews the strategies for screening attractive DNAzymes such as SELEX and high-throughput sequencing, and briefly describes the amplification strategies of DNAzymes, which mainly include catalytic hairpin assembly (CHA), DNA walker, hybridization chain reaction (HCR), DNA origami, CRISPR-Cas12a, rolling circle amplification (RCA), and aptamers. In addition, applications of DNAzymes in bioimaging, biosensing, and cancer therapy are also highlighted. Subsequently, the possible challenges of these DNAzymes in practical applications are further pointed out, and future research directions are suggested.

mHealth Physical Activity and Patient-Reported Outcomes in Patients With Inflammatory Bowel Diseases: Cluster Analysis.

BACKGROUND: Regular physical activity is associated with improved quality of life in patients with inflammatory bowel diseases (IBDs), although much of the existing research is based on self-reported data. Wearable devices provide objective data on many rich physical activity dimensions including steps, duration, distance, and intensity. Little is known about how patients with IBDs engage in these varying dimensions of exercise and how it may influence their symptom and disease-specific patient-reported outcomes (PROs). OBJECTIVE: This study aims to (1) cluster physical activity patterns from consumer-grade wearable devices and (2) assess the relationship between the clusters and PROs in patients with IBDs. METHODS: We conducted a cross-sectional and longitudinal cohort study among adults with IBDs in the Crohn's and Colitis Foundation IBD Partners cohort. Participants contribute physical activity data through smartphone apps or wearable devices in a bring-your-own-device model. Participants also complete biannual PRO questionnaires from the Patient-Reported Outcomes Measurement Information System short forms and IBD-specific questionnaires. K-means cluster analysis was used to generate physical activity clusters based on 3 key features: number of steps, duration of moderate to vigorous activity (minutes), and distance of activity (miles). Based on the clusters, we conducted a cross-sectional analysis to examine differences in mean questionnaire scores and participant characteristics using one-way ANOVA and chi-square tests. We also conducted a longitudinal analysis to examine individual cluster transitions among participants who completed multiple questionnaires, and mean differences in questionnaire scores were compared using 2-tailed paired sample t tests across 6-month periods. RESULTS: Among 430 participants comprising 1255 six-week physical activity periods, we identified clusters of low (33.7%, n=423), moderate (46%, n=577), and high (20.3%, n=255) physical activity. Scores varied across clusters for depression (P=.004), pain interference (P<.001), fatigue (P<.001), sleep disturbance (P<.001), social satisfaction (P<.001), and short Crohn Disease Activity Index (P<.001), with those in the low activity cluster having the worst scores. Sociodemographic characteristics also differed, and those with low physical activity were older (P=.002), had higher BMIs (P<.001), and had longer disease durations (P=.02) compared to other clusters. Among 246 participants who completed at least 2 consecutive questionnaires consisting of 726 questionnaire periods, 67.8% (n=492) remained in the same cluster, and only 1.2% (n=9) moved to or from the furthest clusters of low and high activity across 6-month periods. CONCLUSIONS: For patients with IBDs, there were positive associations between physical activity and PROs related to disease activity and psychosocial domains. Physical activity patterns mostly did not fluctuate over time, suggesting little variation in exercise levels in the absence of an intervention. The use of real-world data to identify subgroups with similar lifestyle behaviors could be leveraged to develop targeted interventions that provide support for psychosocial symptoms and physical activity for personalized IBD care.

Serum Fructosamine as an Indicator of Perioperative Complications in Patients Undergoing Foot and Ankle Surgery.

Background: Patients with poor glycemic control are at increased risk of postoperative complications. Hemoglobin A1c (HbA1c) has traditionally been used to assess preoperative glycemic control, but with limitations. More recently, fructosamine has been tested preoperatively in patients undergoing elective total joint arthroplasty. This study aims to assess whether preoperative serum fructosamine can be used to avoid adverse outcomes in patients undergoing foot and ankle surgery. Methods: This was a retrospective chart review of all patients who underwent foot and ankle surgeries at 2 level 1 trauma centers from January 2020 to December 2021. Of those, 305 patients were tested for HbA1c and fructosamine levels preoperatively. Adverse outcomes were assessed over 30 and 90 days. Outcomes of interest were surgical site infection, wound dehiscence, unplanned return to the operating room, unplanned readmission, and death. Data were analyzed using independent 2-sample t tests. A mixed effects model was used for multivariate analysis. P values less than .05 were considered statistically significant. Results: Preoperative serum fructosamine was significantly higher (P = .029) in those with complications within 90 days compared to those without. The mean preoperative fructosamine level was 269.2 µmol/L (SD = 58.85) in those who did have a complication vs 247.2 µmol/L (SD = 53.95) in those who did not. Clinically significant fructosamine threshold was determined using 2 different methods. Fructosamine was found to be non-inferior to HbA1c in accurately predicting postoperative complications. Conclusion: Fructosamine is a serum marker that reflects nearer term glycemic control than HbA1c. Elevation in preoperative fructosamine is associated with increased perioperative complications after foot and ankle surgery within 90 days. Preoperative fructosamine may be used in patient optimization and risk stratification when determining candidacy and timing for elective foot and ankle surgeries. Level of evidence: Level III, retrospective cohort study.

A two-year prospective study to compare the peri-implant parameters of posterior implant-supported single crowns with and without mesial proximal contact loss.

Background/purpose: Interproximal contact loss may lead to food impaction and result in subsequently periodontal complications. The purpose of this prospective study was to investigate the peri-implant parameters of posterior implant-supported single crowns (SCs) with and without mesial proximal contact loss after 2 years of follow-up. Material and methods: Twenty-six patients with a total of 40 posterior implant-supported SCs with mesial adjacent natural teeth were observed for 24 months after crown insertion. The mesial proximal contacts were assessed by dental floss, then were classified as tight, weak, and open contacts. The following peri-implant parameters were evaluated, including modified plaque index (MPI), modified gingival index (MGI), and probing depth (PD) were conducted at six sites per tooth (mesiofacail, midfacial, distofacial, mesiolingual, mid-lingual and distolingual) in the 6-, 12-, 18- and 24-month following visits. Furthermore, radiographs were taken regularly in 12- and 24-month recall sections for measuring the marginal bone loss (MBL). Results: At 12-month observation, the incidence rates of weak and open contacts were 22.5 % and 12.5 %; whereas after 24 months of clinical service, the rates came up with 12.9 % and 25.6 %, respectively. No significant differences were found between the tight, weak, and open contact groups in the parameters of MPI, MGI, or PD (P > 0.05) at 12- and 24-month follow-up. None of the mean differences of the peri-implant parameters: MPI, MGI, PD and MBL had significant differences between the tight, weak, and open contact groups after 1 and 2 years of clinical service (P > 0.05). Conclusion: The presence of open, weak, and tight mesial proximal contacts had no significant effects on the peri-implant tissue conditions.

Protocol for a Study Investigating Context-Specific Sedentary Behaviors and Cardiometabolic Health in College-Based Young Adults (CONTEXT-SB).

Background: Sedentary behavior (SB) is detrimental to cardiometabolic disease (CMD) risk, which can begin in young adulthood. To devise effective SB-CMD interventions in young adults, it is important to understand which context-specific sedentary behaviors (CS-SB) are most detrimental for CMD risk, the lifestyle behaviors that co-exist with CS-SBs, and the socioecological predictors of CS-SB. Methods: This longitudinal observational study will recruit 500 college-aged (18-24 years) individuals. Two laboratory visits will occur, spaced 12 months apart, where a composite CMD risk score (e.g., arterial stiffness, metabolic and inflammatory biomarkers, heart rate variability, and body composition) will be calculated, and questionnaires to measure lifestyle behaviors and different levels of the socioecological model will be administered. After each visit, total SB (activPAL) and CS-SB (television, transportation, academic/ occupational, leisure computer, "other"; ecological momentary assessment) will be measured across seven days. Discussion: It is hypothesized that certain CS-SB will show stronger associations with CMD risk, compared to T-SB, even after accounting for coexisting lifestyle behaviors. It is expected that a range of intra-individual, inter-individual, and physical environment socioecological factors will predict CS-SB. The findings from this study will support the development of an evidence-based, multi-level intervention to target SB reduction and mitigate CMD risk in CBYA.

Trends in Continuation of Long-Acting Reversible Contraception Among Adolescents Receiving Medicaid.

PURPOSE: Despite increasing use of long-acting reversible contraception (LARC) among U.S. adolescents, there is limited literature on factors affecting intrauterine device (IUD) or subdermal implant use. This study aimed to describe statewide rates, and associated patient and provider factors of adolescent IUD or implant initiation and continuation. METHODS: This retrospective cohort study used N.C. Medicaid claims data. 10,408 adolescents were eligible (i.e., 13-19 years, female sex, continuous Medicaid enrollment, had an IUD or implant insertion or removal code from January 1, 2013, to October 1, 2015). Bivariate analyses assessed differences in adolescents using IUD versus implant. Kaplan-Meier curves were created to assess IUD or implant discontinuation through December 31, 2018. RESULTS: Adolescents initiated 8,592 implants and 3,369 IUDs (N = 11,961). There were significant differences in nearly all provider and patient factors for those who initiated implants versus IUDs. 16% of implants and 53% of IUDs were removed in the first year. Younger (i.e., age <18 years old), Hispanic, and Black adolescents had higher adjusted continuation of implants compared with older and White adolescents, respectively (both p < .001). Those whose IUD was inserted by an obstetrician/gynecologist provider had lower continuation of IUDs compared with non-obstetrician/gynecologist providers (p < .001). DISCUSSION: We found that age-related, racial, and ethnic disparities exist in both implant and IUD continuation. Practice changes to support positive adolescent experiences with implant and IUD insertion and removals are needed, including patient-centered health care provider training in contraception counseling, LARC initiation and removal training for adolescent-facing providers, and broader clinic capacity for LARC services.

3D-printed Bi2Te3-based Thermoelectric Generators for Energy Harvesting and Temperature Response.

Thermoelectric generators (TEGs) are environmentally friendly energy harvesting technologies that hold great promise in the field of self-powered electronics and sensing. However, the current development of thermoelectric (TE) devices has largely lagged behind the development of thermoelectric materials, especially in the preparation of thermoelectric components with customizable shapes and excellent properties, which largely limits their practical applications. These issues can be effectively addressed by using 3D printing technology. Here, we print multiple p-type thermoelectric legs (pins) consecutively with this simple technique, and the printed TEGs have excellent thermal potential (288 µV K-1 at room temperature) and excellent temperature response properties, which exhibited an output voltage of 127.94 mV at a temperature difference (ΔT) of 40 K. The 3D-printed thermoelectric generator enables the collection of thermal energy. In addition, the device has excellent temperature sensing characteristics, and this temperature signal to electrical signal conversion is very rapid, which enables temperature sensing alarms in a wide temperature domain. Combining these features, an energy harvesting and electrical alarm concept for home-scale applications is proposed, which is expected to provide a diverse research idea for the application of next-generation thermoelectric devices.

The utility of home blood pressure load in predicting average self-measured blood pressure.

OBJECTIVES: Average values for self-measured blood pressure (SMBP) more accurately reflect a patient's risk of cardiovascular disease than do office measurements. Oftentimes, however, patients provide lists of individual home blood pressure (BP) measurements, and average values cannot be computed within the time constraints of a clinic visit. In contrast, the home BP load - defined as the proportion of BP values greater than a partition value (e.g., 130 mmHg) - can be easily calculated. We examined the utility of the BP load in predicting the mean SMBP and confirming elevated SMBP. METHODS: Four hundred twenty untreated adults at least 30 years of age acquired SMBP data twice in the morning and twice in the evening over 10 days. The 'true' SMBP was defined as the mean of these 40 determinations. RESULTS: Using all 10 days of BP data and a systolic BP threshold of 130 mmHg, the average SMBP associated with a home BP load of 0.50 was 130 mmHg, with a 95% prediction interval of 126-133 mmHg. True systolic SMBP was approximately 6 mmHg lower and higher at home BP loads of 0.25 and 0.75, respectively. There was a 90% probability that the true systolic SMBP was greater than 130 mmHg if the systolic home BP load was at least 0.60. Corresponding values for 3 days and 1 day of SMBP were at least 0.68 and at least 0.84, respectively. CONCLUSION: Our analysis demonstrates that the home BP load can be used to estimate the average BP acquired on home monitoring and confirm elevated SMBP.

Pre-post-evaluation of a dementia-specific advance care planning toolkit for Japanese primary care clinicians.

BACKGROUND: The population of people living with dementia (PLwD) continues to grow in Japan where advance care planning (ACP) for PLwD is relatively new. Our aim was to evaluate the feasibility and cultural acceptability of a dementia-specific ACP communication skills toolkit for Japanese primary care clinicians. METHODS: We delivered 13 training sessions in primary care clinics across central Japan and conducted a post-training survey to assess whether the toolkit increased confidence in dementia-specific ACP communication skills and the acceptability of the toolkit with the following four statements: (1) The language in the sessions was clear, (2) The sessions took an appropriate amount of time to complete, (3) The design of the sessions was an effective educational method, and (4) The sessions were culturally appropriate for communication with Japanese patients with dementia and their family members. We asked participants to respond using a 5-point Likert scale from strongly agree to strongly disagree. RESULTS: All participants were Japanese and included 80 physicians (mean age 39.8 years), 33 nurses (mean age 45.7 years), and 58 other participants (mean age 42.9 years), who were 30.0%, 87.9%, and 55.2% female, respectively. Most participants practiced in rural settings. In pre- post-comparisons, participant confidence increased in determining capacity, understanding dementia prognosis, goals of care, eliciting surrogates, recommending self-care practices to families, and leading family meetings (all p < 0.001). Most participants strongly agreed or agreed that the toolkit was an effective method (96.9%), took an appropriate amount of time (94.5%), contained clear language (89.8%), and was culturally appropriate (73.6%). CONCLUSIONS: Dementia-specific ACP communication skills toolkit can be delivered in Japan. Japanese primary care clinicians generally felt the dementia-specific ACP toolkit increased their confidence in ACP communication skills and was acceptable. The language, time, and design were well received, though further work is needed to improve the cultural appropriateness of the toolkit.

Cultural Connection and Well-being for American Indian Adolescents.

American Indian and Alaska Native (AI/AN) adolescents face health disparities resulting from historical traumas. There is a paucity of research focusing on mental health in AI/AN adolescents or the relationship between cultural connection and health. This project assesses the relationship between cultural identity and markers of mental health and well-being for AI/AN adolescents. Adolescents 12 to 18 years old from the Lumbee Tribe of North Carolina participated in this mixed-methods study. Phase 1, discussed in this manuscript, involved surveys using validated instruments to assess cultural connection and markers of mental health and well-being. Characteristics of the 122 AI/AN youth who completed the survey included: mean age 14.9 years (SD = 2.0); 61% (n = 75) assigned female at birth; 56% (n = 70) identified as female; and 4.1% (n = 5) identified as non-binary. Mean tribal affiliation (TA) and ethnic identity (EI) scores suggest strong cultural connection (TA: M = 3.1/5, SD = 0.6; EI: M = 3.4/5, SD = 0.9). Sleep quality (M = 2.63/5) and positive stress management (M = 2.06/5) were low. Bivariate and logistic regression demonstrated moderate positive correlations between EI and friendship, EI and emotional support, TA and friendship, and TA and emotional support. AI/AN adolescents in this sample have a moderate-strong connection with Native culture, marked by ethnic identity and tribal affiliation, and positive markers of mental health and well-being. Data from this study may be used for policy formulation to promote increased funding and programming addressing mental health for AI/AN youth.

Microheterogeneity of Transmission Shapes Submicroscopic Malaria Carriage in Coastal Tanzania.

BACKGROUND: Asymptomatic carriage of malaria parasites persists even as malaria transmission declines. Low-density infections are often submicroscopic, not detected with rapid diagnostic tests (RDTs) or microscopy but detectable by polymerase chain reaction (PCR). METHODS: To characterize submicroscopic Plasmodium falciparum carriage in an area of declining malaria transmission, asymptomatic persons >5 years of age in rural Bagamoyo District, Tanzania, were screened using RDT, microscopy, and PCR. We investigated the size of the submicroscopic reservoir of infection across villages, determined factors associated with submicroscopic carriage, and assessed the natural history of submicroscopic malaria over 4 weeks. RESULTS: Among 6076 participants, P. falciparum prevalences by RDT, microscopy, and PCR were 9%, 9%, and 28%, respectively, with roughly two-thirds of PCR-positive individuals harboring submicroscopic infection. Adult status, female sex, dry season months, screened windows, and bed net use were associated with submicroscopic carriage. Among 15 villages encompassing 80% of participants, the proportion of submicroscopic carriers increased with decreasing village-level malaria prevalence. Over 4 weeks, 23% of submicroscopic carriers (61 of 266) became RDT positive, with half exhibiting symptoms, while half (133 of 266) were no longer parasitemic at the end of 4 weeks. Progression to RDT-positive patent malaria occurred more frequently in villages with higher malaria prevalence. CONCLUSIONS: Microheterogeneity in transmission observed at the village level appears to affect both the size of the submicroscopic reservoir and the likelihood of submicroscopic carriers developing patent malaria in coastal Tanzania.

A Multi-state Non-Markov Framework to Estimate Progression of Chronic Disease.

In chronic disease epidemiology, investigation of disease etiology has largely focused on one single endpoint, and progression of chronic disease as a multi-state process is understudied, representing a knowledge gap. Most of existing multi-state regression models require Markov assumption and are unsuitable to estimate progression of chronic diseases that is largely non-memoryless. We propose a new non-Markov framework that allows past states to affect transition rates of current states. The key innovation is that we convert a non-Markov to Markov process by dividing disease states into substates through conditioning on past disease history. Specifically, we apply cause-specific Cox models (CSC) including past states as covariates to obtain transition rates (TR) of substates, which were used to obtain transition probabilities (TP) and state occupational probabilities (SOP) of substates. We applied our model to describe progression of coronary heart disease (CHD) in the ARIC study, where CHD was modeled in healthy, in risk, CHD, heart failure, and mortality states. We presented transition rates, transition probabilities, and state occupational probabilities between states from age 45 to 95 years. In summary, the significance of our framework lies in that transition parameters between disease substates may shed light on new mechanistic insight of chronic disease and may provide more accurate description of non-Markov process than Markov regression models. Our method has potential of wide application in chronic disease epidemiology.

Liquid-colloid-solid modular assembly for three-dimensional electrochemical biosensing of small molecules.

Electrochemical biosensors hold promise for advanced analytical applications in modern life analysis due to their miniaturization and cost-effectiveness. Nevertheless, their implementation in complex biological systems necessitates overcoming challenges related to timeliness, sensitivity, and interference resistance. Here, we developed a novel DNA hydrogel three-dimensional electron transporter through liquid-colloid-solid assembly, integrating electronic mediators and employing porous electrode covers with 3D printing technology. Our approach facilitated the fabrication of a high-performance electrochemical sensor for small molecule detection, leveraging target-specific aptamers and catalytic hairpin assembly (CHA) elements within the DNA hydrogel, which exhibited outstanding selectivity, sensitivity, and universality, achieving detection limits of 0.047 nM for kanamycin and 2.67 pM for ATP. Furthermore, this sensor could detect kanamycin in real samples, demonstrating good accuracy and robust anti-interference capabilities in human serum. Our work not only possesses substantial application value in clinical sample analysis but also represents a breakthrough in traditional strategies, thereby contributing to advancements in the application of electrochemical biosensors for life analysis.

Preparation of S-C3N4/AgCdS Z-Scheme Heterojunction Photocatalyst and Its Effectively Improved Photocatalytic Performance.

In this study, S-doped graphitic carbon nitride (S-C3N4) was prepared using the high-temperature polymerization method, and then S-C3N4/AgCdS heterojunction photocatalyst was obtained using the chemical deposition method through loading Ag-doped CdS nanoparticles (AgCdS NPs) on the surface of S-C3N4. Experimental results show that the AgCdS NPs were evenly dispersed on the surface of S-C3N4, indicating that a good heterojunction structure was formed. Compared to S-C3N4, CdS, AgCdS and S-C3N4/CdS, the photocatalytic performance of S-C3N4/AgCdS has been significantly improved, and exhibits excellent photocatalytic degradation performance of Rhodamine B and methyl orange. The doping of Ag in collaboration with the construction of a Z-scheme heterojunction system promoted the effective separation and transport of the photogenerated carriers in S-C3N4/AgCdS, significantly accelerated its photocatalytic reaction process, and thus improved its photocatalytic performance.

Catalytic hairpin assembly-based AIEgen/graphene oxide nanocomposite for fluorescence-enhanced and high-precision spatiotemporal imaging of microRNA in living cells.

The low abundance, heterogeneous expression, and temporal changes of miRNA in different cellular locations pose significant challenges for both the detection sensitivity of miRNA liquid biopsy and intracellular imaging. In this work, we report an intelligently assembled biosensor based on catalytic hairpin assembly (CHA) and aggregation-induced emission (AIE), named as catalytic hairpin aggregation-induced emission (CHAIE), for the ultrasensitive detection and intracellular imaging of miRNA-155. To achieve such goal, tetraphenylethylene-N3 (TPE-N3) is used as AIE luminogen (AIEgen), while graphene oxide is introduced to quench the fluorescence. When the target miRNA is present, CHA reaction is triggered, causing the AIEgen to self-assemble with the hairpin DNA. This will restrict the intramolecular rotation of the AIEgen and produce a strong AIE fluorescence. Interestingly, CHAIE does not require any enzyme or expensive thermal cycling equipment, and therefore provides a rapid detection. Under optimal conditions, the proposed biosensor can determine miRNA in the concentration range from 2 pM to 200 nM within 30 min, with the detection limit of 0.42 pM. The proposed CHAIE biosensor in this work offers a low background signal and high sensitivity, making it applicable for highly precise spatiotemporal imaging of target miRNA in living cells.

Threonine dehydrogenase regulates neutrophil homeostasis but not H3K4me3 levels in zebrafish.

l-threonine dehydrogenase (Tdh) is an enzyme that links threonine metabolism to epigenetic modifications and mitochondria biogenesis. In vitro studies show that it is critical for the regulation of trimethylation of histone H3 lysine 4 (H3K4me3) levels and cell fate determination of mouse embryonic stem cells (mESCs). However, whether Tdh regulates a developmental process in vivo and, if it does, whether it also primarily regulates H3K4me3 levels in this process as it does in mESCs, remains elusive. Here, we revealed that, in zebrafish hematopoiesis, tdh is preferentially expressed in neutrophils. Knockout of tdh causes a decrease in neutrophil number and slightly suppresses their acute injury-induced migration, but, unlike the mESCs, the level of H3K4me3 is not evidently reduced in neutrophils sorted from the kidney marrow of adult tdh-null zebrafish. These phenotypes are dependent on the enzymatic activity of Tdh. Importantly, a soluble supplement of nutrients that are able to fuel the acetyl-CoA pool, such as pyruvate, glucose and branched-chain amino acids, is sufficient to rescue the reduction in neutrophils caused by tdh deletion. In summary, our study presents evidence for the functional requirement of Tdh-mediated threonine metabolism in a developmental process in vivo. It also provides an animal model for investigating the nutritional regulation of myelopoiesis and immune response, as well as a useful tool for high-throughput drug/nutrition screening.