LncRNA CCAT1 knockdown suppresses tongue squamous cell carcinoma progression by inhibiting the ubiquitination of PHLPP2.

Tongue squamous cell carcinoma (TSCC) is prevailing malignancy in the oral and maxillofacial region, characterized by its high frequency. LncRNA CCAT1 can promote tumorigenesis and progression in many cancers. Here, we investigated the regulatory mechanism by which CCAT1 influences growth and metastasis of TSCC. Levels of CCAT1, WTAP, TRIM46, PHLPP2, AKT, p-AKT, and Ki67 in TSCC tissues and cells were assessed utilizing qRT-PCR, Western blot and IHC. Cell proliferation, migration, and invasion were evaluated utilizing CCK8, colony formation, wound healing and transwell assays. Subcellular localization of CCAT1 was detected utilizing FISH assay. m6A level of CCAT1 was assessed using MeRIP. RNA immunoprecipitation (RIP), Co-immunoprecipitation (Co-IP) and RNA pull down elucidated binding relationship between molecules. Nude mouse tumorigenesis experiments were used to verify the TSCC regulatory function of CCAT1 in vivo. Metastatic pulmonary nodules were observed utilizing hematoxylin and eosin (HE) staining. CCAT1 silencing repressed TSCC cell proliferation, migration and invasion. Expression of CCAT1 was enhanced through N6-methyladenosine (m6A) modification of its RNA, facilitated by WTAP. Moreover, IGF2BP1 up-regulated CCAT1 expression by stabilizing its RNA transcript. CCAT1 bond to PHLPP2, inducing its ubiquitination and activating AKT signaling. CCAT1 mediated the ubiquitination and degradation of PHLPP2 by TRIM46, thereby promoting TSCC growth and metastasis. CCAT1/TRIM46/PHLPP2 axis regulated proliferation and invasion of TSCC cells, implying that CCAT1 would be a novel therapeutic target for TSCC patients.

Analysis of epigenetic features characteristic of L1 loci expressed in human cells.

Only a select few L1 loci in the human genome are expressed in any given cell line or organ, likely to minimize damage done to the genome. The epigenetic features and requirements of expressed L1 loci are currently unknown. Using human cells and comprehensive epigenetic analysis of individual expressed and unexpressed L1 loci, we determined that endogenous L1 transcription depends on a combination of epigenetic factors, including open chromatin, activating histone modifications, and hypomethylation at the L1 promoter. We demonstrate that the L1 promoter seems to require interaction with enhancer elements for optimal function. We utilize epigenetic context to predict the expression status of L1Hs loci that are poorly mappable with RNA-Seq. Our analysis identified a population of 'transitional' L1 loci that likely have greater potential to be activated during the epigenetic dysregulation seen in tumors and during aging because they are the most responsive to targeted CRISPR-mediated delivery of trans-activating domains. We demonstrate that an engineered increase in endogenous L1 mRNA expression increases Alu mobilization. Overall, our findings present the first global and comprehensive analysis of epigenetic status of individual L1 loci based on their expression status and demonstrate the importance of epigenetic context for L1 expression heterogeneity.

Generalization Enhancement of Visual Reinforcement Learning through Internal States.

Visual reinforcement learning is important in various practical applications, such as video games, robotic manipulation, and autonomous navigation. However, a major challenge in visual reinforcement learning is the generalization to unseen environments, that is, how agents manage environments with previously unseen backgrounds. This issue is triggered mainly by the high unpredictability inherent in high-dimensional observation space. To deal with this problem, techniques including domain randomization and data augmentation have been explored; nevertheless, these methods still cannot attain a satisfactory result. This paper proposes a new method named Internal States Simulation Auxiliary (ISSA), which uses internal states to improve generalization in visual reinforcement learning tasks. Our method contains two agents, a teacher agent and a student agent: the teacher agent has the ability to directly access the environment's internal states and is used to facilitate the student agent's training; the student agent receives initial guidance from the teacher agent and subsequently continues to learn independently. From another perspective, our method can be divided into two phases, the transfer learning phase and traditional visual reinforcement learning phase. In the first phase, the teacher agent interacts with environments and imparts knowledge to the vision-based student agent. With the guidance of the teacher agent, the student agent is able to discover more effective visual representations that address the high unpredictability of high-dimensional observation space. In the next phase, the student agent autonomously learns from the visual information in the environment, and ultimately, it becomes a vision-based reinforcement learning agent with enhanced generalization. The effectiveness of our method is evaluated using the DMControl Generalization Benchmark and the DrawerWorld with texture distortions. Preliminary results indicate that our method significantly improves generalization ability and performance in complex continuous control tasks.

Organ-, sex- and age-dependent patterns of endogenous L1 mRNA expression at a single locus resolution.

Expression of L1 mRNA, the first step in the L1 copy-and-paste amplification cycle, is a prerequisite for L1-associated genomic instability. We used a reported stringent bioinformatics method to parse L1 mRNA transcripts and measure the level of L1 mRNA expressed in mouse and rat organs at a locus-specific resolution. This analysis determined that mRNA expression of L1 loci in rodents exhibits striking organ specificity with less than 0.8% of loci shared between organs of the same organism. This organ specificity in L1 mRNA expression is preserved in male and female mice and across age groups. We discovered notable differences in L1 mRNA expression between sexes with only 5% of expressed L1 loci shared between male and female mice. Moreover, we report that the levels of total L1 mRNA expression and the number and spectrum of expressed L1 loci fluctuate with age as independent variables, demonstrating different patterns in different organs and sexes. Overall, our comparisons between organs and sexes and across ages ranging from 2 to 22 months establish previously unforeseen dynamic changes in L1 mRNA expression in vivo. These findings establish the beginning of an atlas of endogenous L1 mRNA expression across a broad range of biological variables that will guide future studies.

CBLC inhibits the proliferation and metastasis of breast cancer cells via ubiquitination and degradation of CTTN.

The E3 ubiquitin ligase is an important regulator of cell signaling and proteostasis and is tightly controlled in many diseases, including cancer. Our study aimed to investigate the biological role of the E3 ubiquitin ligase CBLC in breast cancer and elucidate the specific mechanistic network underlying CBLC-mediated target substrate degradation, cell proliferation and metastasis. Here, we showed that CBLC expression was higher in breast cancer tissues and cells than that in normal tissues and cells. Higher expression of CBLC predicted a better prognosis for breast cancer patients. CBLC inhibited the proliferation, migration and invasion of breast cancer cells. Co-IP and immunofluorescence co-localization assays demonstrated that CBLC interacted with CTTN in the cytoplasm. CBLC promoted the degradation of CTTN through the ubiquitin-proteasome pathway without affecting its mRNA level. The inhibitory effect of CBLC on breast cancer cell proliferation, migration and invasion could partly be reversed by CTTN. Taken together, our study clarified the biological role of CBLC as a tumor suppressor and discovered its functional substrate, providing a molecular basis for CBLC/CTTN as a potential therapeutic target in breast cancer.

Age and sex differences in social support among children and adolescents with epilepsy.

OBJECTIVE: This study aimed to explore what differences exist in the perceived frequency of social support and the importance of social support according to age and sex among children and adolescents with epilepsy. METHOD: We employed an explorative cross-sectional design to examine a sample of 320 children and adolescents with epilepsy using the child and adolescent social support scale (CASSS). RESULT: There is a significant relationship between sex and age and the importance of support from classmates and friends. For the dependent variables that were not affected by the age-sex interaction, we analyzed the main effects of these dependent variables of sex and age separately. We discovered that girls with epilepsy received a higher level of support from their parents and classmates than boys. Besides, compared with adolescents, children with epilepsy consider parental support more valuable. Also, children with epilepsy attach more importance to support from their teachers than adolescents. In contrast, adolescents with epilepsy receive a higher level of support from their friends than children. CONCLUSION: Social support varies by age and sex in children and adolescents with epilepsy. Understanding the social support of children with epilepsy at various developmental stages and for different sexes can help provide a healthier environment for children and adolescents to grow up in. The results of this study provide a basis for formulating corresponding intervention programs for children and adolescents with epilepsy according to age and sex.

Microcephaly family protein MCPH1 stabilizes RAD51 filaments.

Microcephalin 1 (MCPH1) was identified from genetic mutations in patients with primary autosomal recessive microcephaly. In response to DNA double-strand breaks (DSBs), MCPH1 forms damage-induced foci and recruits BRCA2-RAD51 complex, a key component of the DSB repair machinery for homologous recombination (HR), to damage sites. Accordingly, the efficiency of HR is significantly attenuated upon depletion of MCPH1. The biochemical characteristics of MCPH1 and its functional interaction with the HR machinery had remained unclear due to lack of highly purified MCPH1 recombinant protein for functional study. Here, we established a mammalian expression system to express and purify MCPH1 protein. We show that MCPH1 is a bona fide DNA-binding protein and provide direct biochemical analysis of this MCPH family protein. Furthermore, we reveal that MCPH1 directly interacts with RAD51 at multiple contact points, providing evidence for how MCPH1 physically engages with the HR machinery. Importantly, we demonstrate that MCPH1 enhances the stability of RAD51 on single-strand DNA, a prerequisite step for RAD51-mediated recombination. Single-molecule tethered particle motion analysis showed a ∼2-fold increase in the lifetime of RAD51-ssDNA filaments in the presence of MCPH1. Thus, our study demonstrates direct crosstalk between microcephaly protein MCPH1 and the recombination component RAD51 for DSB repair.

Critical Steps to Performing a Successful Single-site Laparoscopic Myomectomy for Large Pedunculated Myoma during Pregnancy.

STUDY OBJECTIVE: To demonstrate tips and tricks for the successful use of single-site laparoscopic surgery for pedunculated myomectomy during pregnancy. DESIGN: Stepwise demonstration with narrated video footage. SETTING: An academic tertiary care hospital affiliated with Baylor College of Medicine. Our patient is a 39-year-old pregnant G1P0010 with a symptomatic 12-cm degenerating pedunculated myoma refractory to conservative pain management. INTERVENTIONS: Recent literature has indicated that most laparotomic myomectomies performed during pregnancy showed overall positive pregnancy outcomes and low complications. This indicates that myomectomy in pregnancy is safe and can be used in cases unresponsive to conservative management [1]. However, cases in literature discussing the single-site techniques for laparoscopic myomectomy during pregnancy have been sparse [2]. Four case series were reviewed; a total of 62 pregnant patients underwent laparoendoscopic single-site surgery without any complications [3-6]. Using laparoscopy in myomectomy compared with laparotomy during pregnancy permits decreased postoperative pain, quicker recovery, and lowered risk of postoperative complications [5,7,8]. Single-site laparoscopic surgery also aids in improved patient cosmesis and can be used for the myoma removal. Literature has demonstrated that single-site laparoscopy is safe and feasible during all stages of pregnancy [3,4]. Nevertheless, this approach may be challenging for inexperienced surgeons owing to the lack of triangulation and crowding of instruments in single-site laparoscopy [5]. At 21 weeks and 3 days pregnancy, our patient underwent single-incision laparoscopic surgery myomectomy. A 2.5-cm skin incision was made at the umbilicus to the abdominal cavity, and a GelPOINT Mini was inserted. Through the laparoscope, we can observe that a 12-cm pedunculated myoma was protruding from the right uterine fundus on a 4-cm stalk. A 0-Vicryl suture was tied around the base of the stalk. The stalk was then cauterized with bipolar energy and transected with the harmonic scalpel, completely detaching the myoma. Subsequently, an Endo Catch bag was placed around the myoma and brought up to the umbilical incision. Using a scalpel, bag-contained morcellation was completed within 22 minutes and the contents removed. As a result, the estimated blood loss was 50 cc and the total operative time was 123 minutes. The extended operating time was caused by slow movements to avoid disrupting the fetus. She had an unremarkable postoperative course, no medications were needed for pain management, and she was discharged home on postoperative day 2. At 38 weeks, she successfully delivered with elective cesarean delivery with no complications. Histopathology showed fragments of leiomyoma with diffuse necrosis. Tips and tricks: 1. Single-site entry technique uses the open Hasson technique, which reduces the risk of injury to the pregnant uterus and dilated surrounding vessels. 2. Through a 2.5-cm incision, the surgeon placed a suture in the myoma stalk because other hemostasis agents such as vasopressin are contraindicated in pregnancy. 3. Owing to difficulties related to single-site surgery, the surgeon should possess extensive expertise in single-site surgery. 4. Manipulation of the uterus should be minimized to reduce the disturbance of the pregnant uterus. 5. V-loc suture allows for faster and simplified uterine incision closure. 6. If the surgeon encounters excessive difficulty during the surgery, a 5-mm accessory port can be placed. 7. During tissue extraction, gentle traction should be used to reduce provoking the pregnant uterus. 8. When transecting the myoma stalk, it is important to leave a stump of more than 1 cm to increase suturing ease and prevent accidental suturing of the uterus. CONCLUSION: Single-incision laparoscopic surgery myomectomy for pedunculated myoma may be a practical technique in women refractive to conservative management. When performed by an experienced surgeon, the patient may benefit from faster specimen removal and recovery.

Nursing perspectives on transitional care between paediatric intensive care units and general wards: A focus group study.

AIM: We aim to explore the experiences of nursing staff in paediatric intensive care units (PICUs) and wards when transporting and caring for patients being discharged from PICU. BACKGROUND: PICU discharge is a challenging and complex procedure with risks and complications for patients. Nursing staff in PICU and paediatric wards play a pivotal role in the transition and are responsible for the quality of care, but their perspectives have rarely been explored. METHODS: Focus groups were conducted between December 2021 and January 2022 with purposively sampled PICU nurses and ward nurses. Four focus groups were formed, and data were analysed using qualitative content analysis. RESULTS: The overarching themes were as follows: communication during handover, attitudes towards follow-up, a challenging transition for nurses and parents and suggestions for optimizing transitional procedure. CONCLUSION: Our findings provide nurses' insights and knowledge regarding the transition of patients from the PICU to the ward. Nursing strategies including the use of liaison nurses and critical training for ward nurses were considered essential to maintaining competence during transition. A well-structured handover checklist as well as interdisciplinary cooperation and transitional care units are important for the patient's quality of care. IMPLICATION FOR NURSING MANAGEMENT: Communication, cooperation, planning and professional care are vital during the transition process. Nurse managers should work to develop collaborative approaches to facilitate safe patient transition.

Parental experience of transition from a paediatric intensive care unit to a general ward: A qualitative study.

AIM: We aim to explore parental experience in transitioning from a paediatric intensive care unit to a general ward and to investigate parental involvement in caring for their critical illness children. BACKGROUND: Parents have a major responsibility in caring for seriously ill children, but nursing staff fail to meet the expectations of parents regarding nursing care. Few studies have investigated the challenges and needs of Chinese parents during the transition from paediatric intensive care unit to general ward. METHODS: Semi-structured interviews were conducted with 24 parents of children with critical illness in a paediatric hospital in Shanghai, mainland China to explore their views. Transcripts were entered into NVivo. Framework analysis was used to analyse the qualitative data. RESULTS: Four themes were identified by data analysis: changes in the child during post paediatric intensive care unit periods; experiencing a wide range of emotions; factors involved in the transition; and suggestions for improving transitional care. CONCLUSIONS: Due to the unmet needs of parents, a more flexible visiting policy and social media support were highly desirable. Getting accurate information, establishing family integrated care, and strengthening ward-based critical support services were also listed as important needs of parents caring for critically ill children. IMPLICATIONS FOR NURSING MANAGEMENT: A profound understanding of parental experiences during the transitional period can help nursing staff to assess the effects on children and their families, improve ward-based intensive care, support parental participation, and improve visitation policies. Based on these findings, nurse managers can develop reasonable intervention programmes in order to improve nursing quality and patient outcomes.

Kerr-lens mode-locked Tm-doped sesquioxide ceramic laser.

Kerr-lens mode-locked solid-state laser operation at ∼2µm is investigated. Using a Tm3+-doped (Lu,Sc)2O3 "mixed" sesquioxide ceramic as a gain medium, pulses as short as 58 fs are generated at ∼2081nm via soft-aperture Kerr-lens mode locking. The average output power amounts to 220 mW at a pulse repetition rate of 84.8 MHz. The emitted spectrum at the long-wavelength wing extends to >2.2µm which is attributed to vibronic transitions of the Tm3+ ions. The latter is found to be essential for generating pulses with durations in the 50 fs range.

Inhibition of the proliferation, migration, and invasion of human breast cancer cells by leucine aminopeptidase 3 inhibitors derived from natural marine products.

Leucine aminopeptidase 3 is involved in the progression and metastasis of several cancers. This study aimed to screen anti-tumor lead compounds targeting leucine aminopeptidase 3. The compounds' suppression effect on enzyme activity and anti-tumor activity were evaluated through a series of assays. Leucine aminopeptidase 3 overexpression K562 cells were used as an enzyme source to screen 43 natural marine compounds. Compounds 5 and 6 exhibited high suppression effect on leucine aminopeptidase 3 activity. Cell activity tests indicated that both compounds have an anti-proliferative effect on triple-negative breast cancer cells. Wound healing assay and transwell invasion assay showed that both compounds could inhibit the migration and invasion of breast cancer cells. Immunoblot analysis exhibited that both compounds could downregulate the expression of metastasis-related proteins fascin and matrix metalloproteinase-2/9. A molecular dynamic simulation process was applied to discover the key features of compounds 5 and 6 in binding to leucine aminopeptidase 3 active site. This study described the anti-tumor effects of two leucine aminopeptidase 3 small molecule inhibitors. Taken together, compounds 5 and 6 could be used as anti-tumor lead compounds targeting leucine aminopeptidase 3.

Characteristics of photonic jets generated by a dielectric sphere illuminated by a Gaussian beam.

Photonic jets (PJs) formed on the shadow side of micro-sized dielectric spheres excited by focused Gaussian beams are investigated within the framework of the generalized Lorenz-Mie theory (GLMT). The intrinsic advantages of rapidity and high accuracy of the GLMT in calculations enable us to conduct a systematic study of PJs at a low cost and a high reliability. To reveal the influence of beam parameters on the properties of PJs, numerical results concerning variations of key parameters of PJs, including the maximal intensity, the focal distance, which is linked to the position of maximal intensity, and longitudinal and transversal dimensions are presented with the change of the beam waist radius and the focal center location of the Gaussian beam. The results show that as the beam waist radius approaches the radius of the particle, the energy stream of the Gaussian beam contributes more efficiently to the formation of PJs. By properly tuning the location of the beam focal center, the PJ pattern can be efficiently engineered to a large extent.

Leucine aminopeptidase 3 promotes migration and invasion of breast cancer cells through upregulation of fascin and matrix metalloproteinases-2/9 expression.

Overexpression of leucine aminopeptidase 3 (LAP3) is involved in proliferation, migration, and invasion of several tumor cells and plays a crucial role in tumor metastasis. However, the related mechanism remains unknown. In this study, we used MDA-MB-231 and MCF7 breast cancer cell lines to explore the role of LAP3 in the regulation of cancer cell migration and invasion by employing the natural LAP3 inhibitor bestatin and a lentivirus vector that overexpresses or knocks down LAP3. Bestatin inhibited tumor cell migration and invasion in a dose-dependent manner. Western blot assay showed that bestatin and knockdown of LAP3 upregulated phosphorylation of Hsp27 and downregulated expression of fascin. Phosphorylation of Akt and expression of matrix metalloproteinase-2/9 can also be downregulated. LAP3 overexpression showed the opposite results. Immunohistochemistry analysis was conducted to detect expression levels of LAP3 in breast cancer tissues. High LAP3 expression was correlated with the grade of malignancy. Findings of this study uncovered the molecular mechanism of LAP3 on breast cancer metastasis and indicated that LAP3 may act as a potential antimetastasis therapeutic target.

New Method for Detecting the Suppressing Effect of Enzyme Activity by Aminopeptidase N Inhibitor.

Aminopeptidase N, also known as CD13, is a transmembrance protease with many functions. CD13 is involved in inflammatory diseases and cancers. A convenient and reliable laboratory test method for detecting the suppressing effects of enzyme activity would be useful for study of CD13 inhibitors. Porcine CD13 (pCD13) was traditionally considered an enzyme source but has significant practical disadvantages. pCD13 is not a human source, and the accuracy and reliability of experimental results are greatly reduced. In this study, a modified detection method with K562-CD13 monoclonal cells, a human-derived cell line, was established to detect the suppressing effects of enzyme activity by the CD13 inhibitor. In this method, K562-CD13 monoclonal cells were used as enzyme source and L-leucine p-nitroaniline hydrochloride as substrate. Using CD13 enzyme activity analyses, we found that the ability of the catalytic substrate was weaker in K562 cells than in the other cell lines, and K562-CD13 cells expressed significantly higher levels of CD13 enzyme activity than parental K562 cells. The enzyme activity of CD13 was detected with the new method after ubenimex treatment. The enzyme activity was significantly inhibited by ubenimex in a dose-dependent manner. In summary, this study proposes a sensitive, stable, and objective laboratory method for detecting the inhibitory effect of the CD13 inhibitor.

Eukaryotic Initiation Factor 3C Can Affect the Proliferation and Invasion of Ovarian Cancer by Regulating the p53 Signalling Pathway.

BACKGROUND: Eukaryotic Initiation Factor 3C (EIF3C) represents a pivotal translational initiation factor in eukaryotes and has been shown to facilitate the progression of various neoplasms. However, its mechanistic role in ovarian cancer remains elusive. METHODS: In this research, the expression of EIF3C in ovarian cancer tissues was investigated using immunohistochemistry. In addition, the assessments were made on changes in cellular proliferation, invasion, and apoptotic abilities by reducing the expression of EIF3C in ovarian cancer cells. By utilizing microarray analysis, a comparison was performed between the downregulated EIF3C group and the control group of ovarian cancer cells, revealing the genes that were expressed differently. Furthermore, the signalling pathways associated with cellular proliferation were validated. The functional role of EIF3C in vivo was investigated using a xenograft tumour model. RESULTS: The immunohistochemical analysis showed that elevated levels of EIF3C are linked to a negative prognosis in patients with ovarian cancer. Suppression of EIF3C greatly hindered the growth and spread of SK-OV-3 and HO-8910 cells while enhancing cellular programmed cell death. Following KEGG and GSEA enrichment analyses of differentially expressed genes, the p53 signalling pathway was found to be associated with EIF3C. Suppression of EIF3C resulted in the upregulation of the p53 signalling pathway, leading to the inhibition of cell proliferation and invasion and the promotion of apoptosis. In vivo experiments demonstrated that EIF3C knockdown suppressed the growth of subcutaneous tumours in nude mice. CONCLUSION: There is a correlation between overexpression of EIF3C in tumour tissues of ovarian cancer patients and this is associated with a poorer prognosis. By influencing the p53 signaling pathway, EIF3C facilitates the growth and infiltration of cells in ovarian cancer.

Pyrroloquinoline quinone promotes human mesenchymal stem cell-derived mitochondria to improve premature ovarian insufficiency in mice through the SIRT1/ATM/p53 pathway.

BACKGROUND: DNA damage and oxidative stress induced by chemotherapy are important factors in the onset of premature ovarian insufficiency (POI). Studies have shown that mitochondria derived from mesenchymal stem cells (MSC-Mito) are beneficial for age-related diseases, but their efficacy alone is limited. Pyrroloquinoline quinone (PQQ) is a potent antioxidant with significant antiaging and fertility enhancement effects. This study aimed to investigate the therapeutic effect of MSC-Mito in combination with PQQ on POI and the underlying mechanisms involved. METHODS: A POI animal model was established in C57BL/6J mice by cyclophosphamide and busulfan. The effects of MSC-Mito and PQQ administration on the estrous cycle, ovarian pathological damage, sex hormone secretion, and oxidative stress in mice were evaluated using methods such as vaginal smears and ELISAs. Western blotting and immunohistochemistry were used to assess the expression of SIRT1, PGC-1α, and ATM/p53 pathway proteins in ovarian tissues. A cell model was constructed using KGN cells treated with phosphoramide mustard to investigate DNA damage and apoptosis through comet assays and flow cytometry. SIRT1 siRNA was transfected into KGN cells to further explore the role of the SIRT1/ATM/p53 pathway in combination therapy with MSC-Mito and PQQ for POI. RESULTS: The combined treatment of MSC-Mito and PQQ significantly restored ovarian function and antioxidant capacity in mice with POI. This treatment also reduced the loss of follicles at various stages, improving the disrupted estrous cycle. In vitro experiments demonstrated that PQQ facilitated the proliferation of MitoTracker-labelled MSC-Mito, synergistically restoring mitochondrial function and inhibiting oxidative stress in combination with MSC-Mito. Both in vivo and in vitro, the combination of MSC-Mito and PQQ increased mitochondrial biogenesis mediated by SIRT1 and PGC-1α while inhibiting the activation of ATM and p53, consequently reducing DNA damage-mediated cell apoptosis. Furthermore, pretreatment of KGN cells with SIRT1 siRNA reversed nearly all the aforementioned changes induced by the combined treatment. CONCLUSIONS: Our research findings indicate that PQQ facilitates MSC-Mito proliferation and, in combination with MSC-Mito, ameliorates chemotherapy-induced POI through the SIRT1/ATM/p53 signaling pathway.

Pediatricians' Perspectives on Introducing Transitional Care into Handover Between Pediatric Intensive Care Units and General Wards.

Background: Despite the availability of a considerable number of studies on transitional care, few qualitative studies have synthesized physicians' perspectives on PICU-to-ward transition to develop a comprehensive transitional care curriculum. The aim of this study is to explore physicians' perceptions and management of the transition of critically ill children from the PICU to the general ward, with the aim of providing an evidence-based curriculum. Methods: A qualitative study was conducted between July and August 2022. The study involved semi-structured interviews with 11 participants, and data analysis was carried out using NVivo 12.0 software through thematic analysis method. Results: Based on the data analysis, three main themes were identified: recognition of professional roles during transition, difficulties during implementation transitional care and suggestions for improving transitional care. Conclusion: The insights of doctors can be valuable in improving transitional care for critically ill children during PICU-to-Ward transition and in developing relevant curricula. It is essential to introduce standardized clinical pathways and strengthen curricula on critical elements, including communication and follow-up.

Skin-interfaced microfluidic sweat collection devices for personalized hydration management through thermal feedback.

Non-electronic wearables that utilize skin-interfaced microfluidic technology have revolutionized the collection and analysis of human sweat, providing valuable biochemical information and indicating body hydration status. However, existing microfluidic devices often require constant monitoring of data during sweat assessment, thereby impeding the user experience and potentially missing anomalous physiological events, such as excessive sweating. Moreover, the complex manufacturing process hampers the scalability and large-scale production of such devices. Herein, we present a self-feedback microfluidic device with a unique dehydration reminder through a cost-effective "CAD-to-3D device" approach. It incorporates two independent systems for sweat collection and thermal feedback, including serpentine microchannels, reservoirs, petal-like bursting valves and heating chambers. The device operates by sequentially collecting sweat in the channels and reservoirs, and then activating thermal stimulators in the heating chambers through breaking the valves, initiating a chemical exothermic reaction. Human trials validate that the devices effectively alert users to potential dehydration by inducing skin thermal sensations triggered by sweat sampling. The proposed device offers facile scalability and customizable fabrication, and holds promise for managing hydration strategies in real-world scenarios, benefiting individuals engaged in sporting activities or exposed to high-temperature settings.

Skin-Interfaced Bifluidic Paper-Based Device for Quantitative Sweat Analysis.

The erratic, intermittent, and unpredictable nature of sweat production, resulting from physiological or psychological fluctuations, poses intricacies to consistently and accurately sample and evaluate sweat biomarkers. Skin-interfaced microfluidic devices that rely on colorimetric mechanisms for semi-quantitative detection are particularly susceptible to these inaccuracies due to variations in sweat secretion rate or instantaneous volume. This work introduces a skin-interfaced colorimetric bifluidic sweat device with two synchronous channels to quantify sweat rate and biomarkers in real-time, even during uncertain sweat activities. In the proposed bifluidic-distance metric approach, with one channel to measure sweat rate and quantify collected sweat volume, the other channel can provide an accurate analysis of the biomarkers based on the collected sweat volume. The closed channel design also reduces evaporation and resists contamination from the external environment. The feasibility of the device is highlighted in a proof-of-the-concept demonstration to analyze sweat chloride for evaluating hydration status and sweat glucose for assessing glucose levels. The low-cost yet highly accurate device provides opportunities for clinical sweat analysis and disease screening in remote and low-resource settings. The developed device platform can be facilely adapted for the other biomarkers when corresponding colorimetric reagents are exploited.