Free-space dissemination of time and frequency with 10-19 instability over 113 km.

Networks of optical clocks find applications in precise navigation1,2, in efforts to redefine the fundamental unit of the 'second'3-6 and in gravitational tests7. As the frequency instability for state-of-the-art optical clocks has reached the 10-19 level8,9, the vision of a global-scale optical network that achieves comparable performances requires the dissemination of time and frequency over a long-distance free-space link with a similar instability of 10-19. However, previous attempts at free-space dissemination of time and frequency at high precision did not extend beyond dozens of kilometres10,11. Here we report time-frequency dissemination with an offset of 6.3 × 10-20 ± 3.4 × 10-19 and an instability of less than 4 × 10-19 at 10,000 s through a free-space link of 113 km. Key technologies essential to this achievement include the deployment of high-power frequency combs, high-stability and high-efficiency optical transceiver systems and efficient linear optical sampling. We observe that the stability we have reached is retained for channel losses up to 89 dB. The technique we report can not only be directly used in ground-based applications, but could also lay the groundwork for future satellite time-frequency dissemination.

Study on the interaction protein of transcription factor Smad3 based on TurboID proximity labeling technology.

TurboID is a highly efficient biotin-labelling enzyme, which can be used to explore a number of new intercalating proteins due to the very transient binding and catalytic functions of many proteins. TGF-ß/Smad3 signaling pathway is involved in many diseases, especially in diabetic nephropathy and inflammation. In this paper, a stably cell line transfected with Smad3 were constructed by using lentiviral infection. To further investigate the function of TGF-ß/Smad3, the protein labeling experiment was conducted to find the interacting protein with Smad3 gene. Label-free mass spectrometry analysis was performed to obtain 491 interacting proteins, and the interacting protein hnRNPM was selected for IP and immunofluorescence verification, and it was verified that the Smad3 gene had a certain promoting effect on the expression of hnRNPM gene, and then had an inhibitory effect on IL-6. It lays a foundation for further study of the function of Smad3 gene and its involved regulatory network.

Optimized Lithium Ion Coordination via Chlorine Substitution to Enhance Ionic Conductivity of Garnet-Based Solid Electrolytes.

Garnet-type solid-state electrolytes attract abundant attentions due to the broad electrochemical window and remarkable thermal stability while their poor ionic conductivity obstructs their widespread application in all-solid-state batteries. Herein, the enhanced ionic conductivity of garnet-type solid electrolytes is achieved by partially substituting O2- sites with Cl- anions, which effectively reduce Li+ migration barriers while preserving the highly conductive cubic phase of garnet-type solid-state electrolytes. This substitution not only weakens the anchoring effect of anions on Li+ to widen the size of Li+ diffusion channel but also optimizes the occupancy of Li+ at different sites, resulting in a substantial reduction of the Li+ migration barrier and a notable improvement in ionic conductivity. Leveraging these advantageous properties, the developed Li6.35 La3 Zr1.4 Ta0.6 O11.85 -Cl0.15 (LLZTO-0.15Cl) electrolyte demonstrates high Li+ conductivity of 4.21×10-6  S cm-1 . When integrated with LiFePO4 (LFP) cathode and metallic lithium anode, the LLZTO-0.15Cl electrolyte enables the solid-state battery to operate for more than 100 cycles with a high capacity retention of 76.61% and superior Coulombic efficiency of 99.48%. This work shows a new strategy for modulating anionic framework to enhance the conductivity of garnet-type solid-state electrolytes.

Perception of visual variance is mediated by subcortical mechanisms.

Variance characterizes the structure of the environment. This statistical concept plays a critical role in evaluating the reliability of evidence for human decision-making. The present study examined the involvement of subcortical structures in the processing of visual variance. To this end, we used a stereoscope to sequentially present two circle arrays in a dichoptic or monocular fashion while participants compared the perceived variance of the two arrays. In Experiment 1, two arrays were presented monocularly to the same eye, dichopticly to different eyes, or binocularly to both eyes. The variance judgment was less accurate in different-eye condition than the other conditions. In Experiment 2, the first circle array was split into a large-variance and a small-variance set, with either the large-variance or small-variance set preceding the presentation of the second circle array in the same eye. The variance of the first array was judged larger when the second array was preceded by the large-variance set in the same eye, showing that the perception of variance was modulated by the visual variance processed in the same eye. Taken together, these findings provide evidence for monocular processing of visual variance, suggesting that subcortical structures capture the statistical structure of the visual world.

Outcomes of antiretroviral treatment for 0-14-year-old children living with HIV in Ganzhou, China, 2006-2023.

BACKGROUND: Studies on antiretroviral therapy (ART) in children living with HIV (CLHIV) are limited due to the small population and low accession rate of ART. METHODS: All 0-14-year-old CLHIV admitted to the Ganzhou Center for Disease Control and Prevention from January 2006 to June 2023 were included retrospectively. The information of treatment regimens, disease progression, and laboratory tests of the patients under ART were used to explore the outcomes and impacts of long-term ART. The normality of all the data was tested by the Shapiro-Wilk test. RESULTS: From 2006 to 2023, 18 CLHIV were reported in Ganzhou. Among them, 11 received ART and were followed up for 60.0 ± 48.4 months. After receiving ART, the median viral load of them decreased from 89,600 copies/ml to 22 copies/ml (P = 0.007), the median CD4+ T cell count increased from 380.7 cells/µL to 661.9 cells/µL (P = 0.028), and the median CD8+ T cell count decreased from 1065.8 cells/µL to 983.3 cells/µL (P = 0.584). The laboratory test results regarding liver function, renal function, blood cell count, and glucolipid metabolism tended to be within normal reference ranges, and the mean height-for-age z-score and weight-for-age z-score increased. However, all the three CLHIV who received cotrimoxazole developed pneumocystis carinii pneumonia, upper respiratory infection, skin lesions, bacterial pneumonia and/or thrush; the mean body-mass-index-for-age z-score decreased from 0.52 to -0.63. CONCLUSION: For CLHIV, ART could effectively inhibit the replication of HIV and improve the immune function of patients. More studies that focus on ART in CLHIV are urgently needed.

Identification and functional study of a novel variant of PAX9 causing tooth agenesis.

OBJECTIVES: To search for pathogenic gene of a family with non-syndromic tooth agenesis, and explore the possible pathogenesis. MATERIALS AND METHODS: A Chinese family with non-syndromic tooth agenesis was recruited and screened for the pathogenic variants by whole exome sequencing technology and co-segregation analysis. The subcellular localization of wild-type and mutant protein was detected by immunofluorescence assay. Cycloheximide chase assay was performed to examine the difference in degradation rate between mutant protein and wild-type one. Dual-luciferase reporter assays were conducted to explore the alterations of mutant protein in the regulation of downstream target genes. RESULTS: A novel missense variant of PAX9 (c.296C>A:p.A99D) was found in this family. Bioinformatics software showed ß-return and the random coil were shortened in the p.A99D. The variant did not affect the subcellular localization of PAX9, but the degradation rate of p.A99D was accelerated (p < 0.05). p.A99D inhibited the activation of downstream target gene BMP4 (p < 0.05). CONCLUSIONS: This novel variant expands the pathogenic gene spectrum. The variant impaired the protein structure, accelerated the degradation of protein, and inhibited the activation of the downstream target gene BMP4, an upstream molecule in the TGF-ß/BMP pathway, which may contribute to tooth agenesis in this family.

A randomized trial of Bacteroides fragilis 839 on preventing chemotherapy-induced myelosuppression and gastrointestinal adverse effects in breast cancer patients.

BACKGROUND AND OBJECTIVES: To evaluate the potential benefits of Bacteroides fragilis 839 (BF839), a next-generation probiotics, in reducing myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patient. METHODS AND STUDY DESIGN: 40 women with early breast cancer were randomly assigned to the BF839 (n=20) or placebo (n=20) during the administration of adjuvant chemotherapy (4 cycles of epirubicin 100mg/m2 and cyclophosphamide 600mg/m2). Myelosuppression and gastrointestinal adverse effects were monitored in both groups. RESULTS: Throughout the four treatment cycles, the percentage of patients experiencing myelosuppression was 42.5% in the BF839 group, significantly lower than the 66.3% observed in the control group (p=0.003). Two patients in the BF839 group and three patients in the placebo group received recombinant human granulocyte colony-stimulating factor (rhG-CSF) due to leuko-penia/neutropenia. When considering an ITT analysis, which included all patients regardless of rhG-CSF treatment, the BF839 group exhibited less reduction from baseline in white blood cells (-0.31±1.19 vs -1.15±0.77, p=0.012) and neutrophils (0.06±1.00 vs -0.84±0.85, p=0.004) compared to the placebo group. The difference became even more significant when excluding the patients who received rhG-CSF injections. Throughout the four treatment cycles, compared to the placebo group, the BF839 group had significantly lower rates of 3-4 grade nausea (35.0% vs 71.3%, p=0.001), vomiting (20.0% vs 45.0%, p=0.001), and diarrhea (15.0% vs 30.0%, p=0.023). CONCLUSIONS: These findings suggest that BF839 has the potential to effectively mitigate myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patients.

Evaluation of bevacizumab biosimilar on wound healing complications in patients with colorectal cancer undergoing endoscopic mucosal resection: A systematic review and meta-analysis in anorectal medicine.

Complications related to wound healing pose substantial obstacle in the management of colorectal cancer (CRC), specifically in the field of anorectal medicine. Biosimilars of bevacizumab have emerged as crucial therapeutic agents in the management of these complications. With the particular emphasis on effects of Bevacizumab Biosimilar Plus on wound healing among patients diagnosed with CRC, this review underscores the potential of this anorectal medication to improve patient outcomes and was aimed to assess the safety and efficacy of Bevacizumab Biosimilar Plus in relation to complications associated with wound healing in patients with CRC. The assessment centers on its therapeutic potential and safety profile within the domain of anorectal medicine. In accordance with the PRISMA guidelines, a comprehensive literature search was performed, resulting in the identification of 19 pertinent studies out of an initial 918. Priority was given to assessing the safety and adverse effects of Bevacizumab Biosimilar Plus in conjunction with its effectiveness in wound healing. The extracted data comprised the following: study design, patient demographics, comprehensive treatment regimens, wound healing-specific outcomes and adverse effects. The evaluation of study quality was conducted utilizing the instruments provided by the Cochrane Collaboration and the Newcastle-Ottawa Scale (NOS). Bevacizumab Biosimilar Plus demonstrates efficacy in the management of wound healing complications among patients with CRC, with a safety and efficacy profile similar to that of the original Bevacizumab, according to the analysis. Notably, several studies reported improved rates of wound healing in relation to the biosimilar. The safety profiles exhibited similarities to the anticipated anti-VEGF agent effects. In wound management, the biosimilar also demonstrated advantages in terms of prolonged efficacy. In addition, analyses of cost-effectiveness suggested that the use of biosimilars could result in cost reductions. Bevacizumab Biosimilar Plus exhibited potential as an anorectal medication for the effective management of wound healing complications in patients with CRC. This has substantial ramifications for improving the quality of patient care, encompassing the affordability and effectiveness of treatments.

Study of FOXO1-interacting proteins using TurboID-based proximity labeling technology.

BACKGROUND: Protein‒protein interactions (PPIs) are the foundation of the life activities of cells. TurboID is a biotin ligase with higher catalytic efficiency than BioID or APEX that reduces the required labeling time from 18 h to 10 min. Since many proteins participate in binding and catalytic events that are very short-lived, it is theoretically possible to find relatively novel binding proteins using the TurboID technique. Cell proliferation, apoptosis, autophagy, oxidative stress and metabolic disorders underlie many diseases, and forkhead box transcription factor 1 (FOXO1) plays a key role in these physiological and pathological processes. RESULTS: The FOXO1-TurboID fusion gene was transfected into U251 astrocytes, and a cell line stably expressing FOXO1 was constructed. While constructing the FOXO1 overexpression plasmid, we also added the gene sequence of TurboID to perform biotin labeling experiments in the successfully fabricated cell line to look for FOXO1 reciprocal proteins. Label-free mass spectrometry analysis was performed, and 325 interacting proteins were found. A total of 176 proteins were identified in the FOXO1 overexpression group, and 227 proteins were identified in the Lipopolysaccharide -treated group (Lipopolysaccharide, LPS). Wild-type U251 cells were used to exclude interference from nonspecific binding. The FOXO1-interacting proteins hnRNPK and RBM14 were selected for immunoprecipitation and immunofluorescence verification. CONCLUSION: The TurboID technique was used to select the FOXO1-interacting proteins, and after removing the proteins identified in the blank group, a large number of interacting proteins were found in both positive groups. This study lays a foundation for further study of the function of FOXO1 and the regulatory network in which it is involved.

Nrf2 regulates iron-dependent hippocampal synapses and functional connectivity damage in depression.

Neuronal iron overload contributes to synaptic damage and neuropsychiatric disorders. However, the molecular mechanisms underlying iron deposition in depression remain largely unexplored. Our study aims to investigate how nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) ameliorates hippocampal synaptic dysfunction and reduces brain functional connectivity (FC) associated with excessive iron in depression. We treated mice with chronic unpredictable mild stress (CUMS) with the iron chelator deferoxamine mesylate (DFOM) and a high-iron diet (2.5% carbonyl iron) to examine the role of iron overload in synaptic plasticity. The involvement of Nrf2 in iron metabolism and brain function was assessed using molecular biological techniques and in vivo resting-state functional magnetic resonance imaging (rs-fMRI) through genetic deletion or pharmacologic activation of Nrf2. The results demonstrated a significant correlation between elevated serum iron levels and impaired hippocampal functional connectivity (FC), which contributed to the development of depression-induced CUMS. Iron overload plays a crucial role in CUMS-induced depression and synaptic dysfunction, as evidenced by the therapeutic effects of a high-iron diet and DFOM. The observed iron overload in this study was associated with decreased Nrf2 levels and increased expression of transferrin receptors (TfR). Notably, inhibition of iron accumulation effectively attenuated CUMS-induced synaptic damage mediated by downregulation of brain-derived neurotrophic factor (BDNF). Nrf2-/- mice exhibited compromised FC within the limbic system and the basal ganglia, particularly in the hippocampus, and inhibition of iron accumulation effectively attenuated CUMS-induced synaptic damage mediated by downregulation of brain-derived neurotrophic factor (BDNF). Activation of Nrf2 restored iron homeostasis and reversed vulnerability to depression. Mechanistically, we further identified that Nrf2 deletion promoted iron overload via upregulation of TfR and downregulation of ferritin light chain (FtL), leading to BDNF-mediated synapse damage in the hippocampus. Therefore, our findings unveil a novel role for Nrf2 in regulating iron homeostasis while providing mechanistic insights into poststress susceptibility to depression. Targeting Nrf2-mediated iron metabolism may offer promising strategies for developing more effective antidepressant therapies.

Effectiveness of the booster dose of inactivated COVID-19 vaccine against Omicron BA.5 infection: a matched cohort study of adult close contacts.

BACKGROUND: Although COVID-19 vaccines and their booster regimens protect against symptomatic infections and severe outcomes, there is limited evidence about their protection against asymptomatic and symptomatic infections in real-world settings, particularly when considering that the majority of SARS-CoV-2 Omicron infections were asymptomatic. We aimed to assess the effectiveness of the booster dose of inactivated vaccines in mainland China, i.e., Sinopharm (BBIBP-CorV) and Sinovac (CoronaVac), against Omicron infection in an Omicron BA.5 seeded epidemic. METHODS: Based on an infection-naive but highly vaccinated population in Urumqi, China, the study cohort comprised all 37,628 adults who had a contact history with individuals having SARS-CoV-2 infections, i.e., close contacts, between August 1 and September 7, 2022. To actively detect SARS-CoV-2 infections, RT-PCR tests were performed by local authorities on a daily basis for all close contacts, and a testing-positive status was considered a laboratory-confirmed outcome. The cohort of close contacts was matched at a ratio of 1:5 with the fully vaccinated (i.e., 2 doses) and booster vaccinated groups (i.e., 3 doses) according to sex, age strata, calendar date, and contact settings. Multivariate conditional logistic regression models were adopted to estimate the marginal effectiveness of the booster dose against Omicron BA.5 infection after adjusting for confounding variables. Subgroup analyses were performed to assess vaccine effectiveness (VE) in different strata of sex, age, the time lag from the last vaccine dose to exposure, and the vaccination status of the source case. Kaplan-Meier curves were employed to visualize the follow-up process and testing outcomes among different subgroups of the matched cohort. FINDINGS: Before matching, 37,099 adult close contacts were eligible for cohort enrolment. After matching, the 2-dose and 3-dose groups included 3317 and 16,051 contacts, and the proportions with Omicron infections were 1.03% and 0.62% among contacts in the 2-dose and 3-dose groups, respectively. We estimated that the adjusted effectiveness of the inactivated booster vaccine versus 2 doses against Omicron infection was 35.5% (95% CI 2.0, 57.5). The booster dose provided a higher level of protection, with an effectiveness of 60.2% (95% CI 22.8, 79.5) for 15-180 days after vaccination, but this VE decreased to 35.0% (95% CI 2.8, 56.5) after 180 days. Evidence for the protection of the booster dose was detected among young adults aged 18-39 years, but was not detected for those aged 40 years or older. INTERPRETATION: The receipt of the inactivated vaccine booster dose was associated with a significantly lower Omicron infection risk, and our findings confirmed the vaccine effectiveness (VE) of booster doses against Omicron BA.5 variants. Given the rapid evolution of SARS-CoV-2, we highlight the importance of continuously monitoring the protective performance of vaccines against the genetic variants of SARS-CoV-2, regardless of existing vaccine coverage.

Transient and fully reversible changes in laboratory parameters and modifications of the cytokine profile during blinatumomab treatment in children with relapsed or refractory B-cell acute lymphoblastic leukemia.

We analyzed changes in laboratory parameters, including blood counts, liver enzymes, inflammation and coagulation markers, and cytokines, from 70 blinatumomab-treated pediatric patients (NCT01471782). Overall, trends were consistent in responders and nonresponders. Platelets and lymphocytes peaked on day (D) 10 in cycle 1 and returned to baseline on D42 and D29, respectively. Neutrophils peaked on D2 and returned to baseline on D42. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin peaked on D17, reversing to baseline on D29; total protein levels were constant. These findings indicate that blinatumomab-induced changes in laboratory parameters were transient, reversible, and not requiring treatment interruptions in responders and nonresponders.

Effects of reminiscence therapy combined with memory specificity training (RT-MeST) on depressive symptoms in older adults: a randomized controlled trial protocol.

BACKGROUND: Geriatric depression has become a serious public health problem, and reduced autobiographical memory and increased overgeneral memory, as the main cognitive markers of depression, are not only associated with current depressive symptoms but also associated with the onset and course of depression, which can lead to a range of harms. Economic and effective psychological interventions are urgently needed. The aim of this study is to confirm the effectiveness of reminiscence therapy combined with memory specificity training in improving autobiographical memory and depressive symptoms in older adults. METHODS: In this multicentre, single-blind, three-arm parallel randomized controlled study, we aim to enrol 78 older adults aged 65 years or older with a score of ≥ 11 on the Geriatric Depression Scale, and participants will be randomly assigned to either a reminiscence therapy group, a reminiscence therapy with memory specificity training group or a usual care group. Assessments will be conducted at baseline (T0) as well as immediately post-intervention (T1) and 1 (T2), 3 (T3) and 6 (T4) months post-intervention. The primary outcome measure is self-reported depressive symptoms, measured using the GDS. Secondary outcome measures include measures of autobiographical memory, rumination, and social engagement. DISCUSSION: We believe that the intervention will play a positive role in improving autobiographical memory and depressive symptoms in older adults. Poor autobiographical memory is a predictor of depression and a major cognitive marker, and improving autobiographical memory is of great significance in alleviating depressive symptoms in older people. If our program is effective, it will provide a convenient and feasible strategy for further promoting healthy ageing. TRIAL REGISTRATION: ChiCTR2200065446.

Comparison of mothers' perceptions of hunger cues in 3-month-old infant under different feeding methods.

BACKGROUND: Mothers' perception of infant hunger cues is a critical content of responsive feeding, which is central to the promotion of early childhood development. However, only a few studies have examined responsive feeding in China, especially lacking the studies on perceptions of infant hunger cues. Consider the cultural differences, the aim of this study was to describe the perceptions of infant hunger cues of Chinese mothers for infants aged 3 months, and explore the relationship between maternal perceptions of infant hunger cues and different feeding methods. METHODS: A cross-sectional study was conducted with a sample of 326 mothers of healthy 3-month-old infants, including 188 exclusive breastfeeding (EBF) mothers and 138 formula feeding (FF) mothers. It was implemented in four provincial and municipal maternal and child health hospitals. The mothers' perceptions of infant hunger cues were surveyed by self-reporting questionnaires. Chi-square tests and logistic analysis were applied to analyze the differences in maternal perceptions of infant hunger cues, including the number of hunger cues and the specific cues, between EBF group and FF group by controlling sociodemographic variables and the daily nursing indicators. RESULTS: We found that a higher proportion of EBF mothers could perceive multiple hunger cues (≥ 2) than FF mothers (66.5% vs.55.1%). For specific cues, the EBF mothers had higher perceptions of infant's "hand sucking" (67.6% vs. 53.6%) and "moving head frantically from side to side" (34.6% vs. 23.9%), all p < 0.05. Regression analysis revealed that EBF might support mothers to perceive infant hunger cues than FF mothers, with the number of infant hunger cues (OR = 1.70, 95% CI: 1.01-2.85), "hand sucking" (OR = 1.72, 95% CI: 1.04-2.87), "moving head frantically from side to side" (OR = 2.07, 95% CI: 1.19-3.62). The number of infant hunger cues perceived by mothers was also associated with their educational level and family structure. CONCLUSION: EBF mothers of 3-month-old infants may be more likely to perceive infant hunger cues than FF mothers in China. It is necessary to increase the health education about infant hunger and satiety cues to caregivers in China, especially among mothers with lower education levels, mothers living in nuclear families, and FF mothers.

Effectiveness of eHealth Interventions on Moderate-to-Vigorous Intensity Physical Activity Among Patients in Cardiac Rehabilitation: Systematic Review and Meta-analysis.

BACKGROUND: Cardiac rehabilitation is a class IA recommendation for patients with cardiovascular diseases. Physical activity is the core component and core competency of a cardiac rehabilitation program. However, many patients with cardiovascular diseases are failing to meet cardiac rehabilitation guidelines that recommend moderate-to-vigorous intensity physical activity. OBJECTIVE: The major objective of this study was to review the evidence of the effectiveness of eHealth interventions in increasing moderate-to-vigorous intensity physical activity among patients in cardiac rehabilitation. The secondary objective was to examine the effectiveness of eHealth interventions in improving cardiovascular-related outcomes, that is, cardiorespiratory fitness, waist circumference, and systolic blood pressure. METHODS: A comprehensive search strategy was developed, and a systematic search of 4 electronic databases (PubMed, Web of Science, Embase, and Cochrane Library) was conducted for papers published from the start of the creation of the database until November 27, 2022. Experimental studies reporting on eHealth interventions designed to increase moderate-to-vigorous intensity physical activity among patients in cardiac rehabilitation were included. Multiple unblinded reviewers determined the study eligibility and extracted data. Risk of bias was evaluated using the Cochrane Collaboration Tool for randomized controlled trials and the Cochrane Effective Practice and Organization of Care group methods for nonrandomized controlled trials. A random-effect model was used to provide the summary measures of effect (ie, standardized mean difference and 95% CI). All statistical analyses were performed using Stata 17. RESULTS: We screened 3636 studies, but only 29 studies were included in the final review, of which 18 were included in the meta-analysis. The meta-analysis demonstrated that eHealth interventions improved moderate-to-vigorous intensity physical activity (standardized mean difference=0.18, 95% CI 0.07-0.28; P=.001) and vigorous-intensity physical activity (standardized mean difference=0.2, 95% CI 0.00-0.39; P=.048) but did not improve moderate-intensity physical activity (standardized mean difference=0.19, 95% CI -0.12 to 0.51; P=.23). No changes were observed in the cardiovascular-related outcomes. Post hoc subgroup analyses identified that wearable-based, web-based, and communication-based eHealth intervention delivery methods were effective. CONCLUSIONS: eHealth interventions are effective at increasing minutes per week of moderate-to-vigorous intensity physical activity among patients in cardiac rehabilitation. There was no difference in the effectiveness of the major eHealth intervention delivery methods, thereby providing evidence that in the future, health care professionals and researchers can personalize convenient and affordable interventions tailored to patient characteristics and needs to eliminate the inconvenience of visiting center-based cardiac rehabilitation programs during the COVID-19 pandemic and to provide better support for home-based maintenance of cardiac rehabilitation. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42021278029; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278029.

Activated Phosphoinositide 3-Kinase δ Syndrome: a Large Pediatric Cohort from a Single Center in China.

PURPOSE: Activated phosphoinositide 3-kinase δ syndrome (APDS) is a primary immunodeficiency first described in 2013, which is caused by gain-of-function mutations in PIK3CD or PIK3R1, and characterized by recurrent respiratory tract infections, lymphoproliferation, herpesvirus infection, autoimmunity, and enteropathy. We sought to review the clinical phenotypes, immunological characteristics, treatment, and prognosis of APDS in a large genetically defined Chinese pediatric cohort. METHODS: Clinical records, radiology examinations, and laboratory investigations of 40 APDS patients were reviewed. Patients were contacted via phone call to follow up their current situation. RESULTS: Sinopulmonary infections and lymphoproliferation were the most common complications in this cohort. Three (10.3%) and five (12.5%) patients suffered localized BCG-induced granulomatous inflammation and tuberculosis infection, respectively. Twenty-seven patients (67.5%) were affected by autoimmunity, while malignancy (7.5%) was relatively rare to be seen. Most patients in our cohort took a combined treatment of anti-infection prophylaxis, immunoglobulin replacement, and immunosuppressive therapy such as glucocorticoid or rapamycin administration. Twelve patients underwent hematopoietic stem cell transplantation (HSCT) and had a satisfying prognosis. CONCLUSION: Clinical spectrum of APDS is heterogeneous. This cohort's high incidence of localized BCG-induced granulomatous inflammation and tuberculosis indicates Mycobacterial susceptibility in APDS patients. Rapamycin is effective in improving lymphoproliferation and cytopenia. HSCT is an option for those who have severe complications and poor response to other treatments.

Coupling W18 O49 /Ti3 C2 Tx MXene Pseudocapacitive Electrodes with Redox Electrolytes to Construct High-Performance Asymmetric Supercapacitors.

A pseudocapacitive electrode with a large surface area is critical for the construction of a high-performance supercapacitor. A 3D and interconnected network composed of W18 O49 nanoflowers and Ti3 C2 Tx MXene nanosheets is thus synthesized using an electrostatic attraction strategy. This composite effectively prevents the restacking of Ti3 C2 Tx MXene nanosheets and meanwhile sufficiently exposes electrochemically active sites of W18 O49 nanoflowers. Namely, this self-assembled composite owns abundant oxygen vacancies from W18 O49 nanoflowers and enough active sites from Ti3 C2 Tx MXene nanosheets. As a pseudocapacitive electrode, it shows a big specific capacitance, superior rate capability and good cycle stability. A quasi-solid-state asymmetric supercapacitor (ASC) is then fabricated using this pseudocapacitive anode and the cathode of activated carbon coupled with a redox electrolyte of FeBr3 . This ASC displays a cell voltage of 1.8 V, a capacitance of 101 F g-1 at a current density of 1 A g-1 , a maximum energy density of 45.4 Wh kg-1 at a power density of 900 W kg-1 , and a maximum power density of 18 000 W kg-1 at an energy density of 10.8 Wh kg-1 . The proposed strategies are promising to synthesize different pseudocapacitive electrodes as well as to fabricate high-performance supercapacitor devices.

Interfacial Electron Redistribution of Hydrangea-like NiO@Ni2 P Heterogeneous Microspheres with Dual-Phase Synergy for High-Performance Lithium-Oxygen Battery.

Lithium-oxygen batteries (LOBs) with ultra-high theoretical energy density (≈3500 Wh kg-1 ) are considered as the most promising energy storage systems. However, the sluggish kinetics during the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) can induce large voltage hysteresis, inferior roundtrip efficiency and unsatisfactory cyclic stability. Herein, hydrangea-like NiO@Ni2 P heterogeneous microspheres are elaborately designed as high-efficiency oxygen electrodes for LOBs. Benefitting from the interfacial electron redistribution on NiO@Ni2 P heterostructure, the electronic structure can be modulated to ameliorate the chemisorption of the intermediates, which is confirmed by density functional theory (DFT) calculations and experimental characterizations. In addition, the interpenetration of the PO bond at the NiO@Ni2 P heterointerface leads to the internal doping effect, thereby boosting electron transfer to further improve ORR and OER activities. As a result, the NiO@Ni2 P electrode shows a low overpotential of only 0.69 V, high specific capacity of 18254.1 mA h g-1 and superior long-term cycling stability of over 1400 h. The exploration of novel bifunctional electrocatalyst in this work provides a new solution for the practical application of LOBs.

Novel mutations of TYK2 leading to divergent clinical phenotypes.

BACKGROUND: TYK2 deficiency is a rare primary immunodeficiency disease caused by loss-of-function mutations of TYK2 gene, which is initially proposed as a subset of hyper-IgE syndrome (HIES). However, accumulating evidence suggests TYK2-deficient patients do not necessarily present with HIES characteristics, indicating a vacuum of knowledge on the exact roles of TYK2 in human immune system. METHOD: Pathogenic effects of patients were confirmed by qRT-PCR, Western blot, and protein stability assays. The responses to cytokines including IFN-α/ß/γ, IL-6, IL-10, IL-12, and IL-23 of peripheral blood mononuclear cells (PBMCs) from these patients were detected by Western blot, qRT-PCR, and flow cytometry. The differentiation of T and B cells was detected by flow cytometry. RESULTS: We described five more TYK2-deficient cases presenting with or without hyper-IgE levels, atopy, and distinct pathogen infection profile, which are caused by novel TYK2 mutations. These mutations were all found by high-throughput sequencing and confirmed by Sanger sequencing. The patients showed heterogeneous responses to various cytokine treatments, including IFN-α/ß/γ, IL-6, IL-10, IL-12, and IL-23. The homeostasis of lymphocytes is also disrupted. CONCLUSION: Based on our findings, we propose that TYK2 works as a multi-tasker in orchestrating various cytokine signaling pathways, differentially combined defects which account for the expressed clinical manifestations.

Intestinal-type adenocarcinoma presenting as a female periurethral mass.

BACKGROUND: The periurethral mass in the female is a rare clinical entity and most of the lesions are benign. We present an unusual case of a periurethral mass found to be intestinal-type adenocarcinoma which has not been previously reported in the literature. CASE PRESENTATION: A 58-year-old woman was referred to our hospital with acute urinary retention. She complained of frequency, urgency and progressive obstructive urinary symptoms for the last 3 months. A pelvic magnetic resonance imaging scan showed a soft tissue mass of 5 × 4 cm surrounding the entire urethra. A needle biopsy was done and revealed adenocarcinoma with intestinal-type features. The tumor was removed by a simultaneous laparoscopic abdominal and transperineal approach. The pathological results showed a positive surgical margin and urethra and vagina wall invasion. The neoplastic cells were positive for CK20, CDX-2, CerbB-2, MSH2, MSH6, MLH1, PMS2 and P53. The patient received adjuvant systemic chemotherapy comprising S-1 and oxaliplatin. Follow-up with pelvic MRI 6 months after surgery showed no signs of local recurrence. CONCLUSIONS: We have reported the first case of the primary periurethral adenocarcinoma of intestinal type. There are currently no standardized protocols for the diagnosis, clinical course, and treatment of this rare tumor. This case study can aid decision-making regarding the diagnosis and treatment of this tumor.