Construction of Hydrophobic Ammonium Perchlorate with Synergistic Catalytic Effect Based on Supramolecular Self-Assembly for Synchronously Catalyzing the Thermal Decomposition of Ammonium Perchlorate and the Combustion of Aluminum.

Ammonium perchlorate (AP), as an important additive component of composite propellants, is critical to the combustion performance of propellants. Herein, AP@1H,1H,2H,2H-perfluorodecyltrichlorosilane (AP@PF) was prepared by establishing a tannic acid-iron ion (TA-Fe) supramolecular self-assembly layer on the AP surface and connecting the 1H,1H,2H,2H-perfluorodecyltrichlorosilane interfacial layer. Results demonstrate that TA-Fe and 1H,1H,2H,2H-perfluorodecyltrichlorosilane are uniformly bound to the surface layer of AP. AP@PF has a lower high-temperature thermal decomposition peak compared to AP. Meanwhile, the exothermic values of low-temperature thermal decomposition (338 J/g) and high-temperature thermal decomposition (597 J/g) of AP@PF are significantly higher than those of AP. In addition, AP@PF exhibits different surface interfacial properties, such as floating on the water surface and exhibiting a static contact angle of 105° on water. AP@PF shows almost no moisture absorption after aging in humid air for 30 days. The exothermic value of the mixture of AP@PF and aluminum powder (156 J/g) is significantly higher than that of the mixture of AP and aluminum (54 J/g), and the mixture of AP@PF and aluminum powder exhibits a higher calorific value and a stronger emission spectrum. Finally, the synergistic catalytic mechanism of AP@PF on the thermal decomposition of AP and the combustion of aluminum powder is also discussed.

Nodules Identified on Surveillance Ultrasound for HCC: CEUS or MRI as the Initial Test?

OBJECTIVES: Following positive surveillance ultrasound (US), magnetic resonance imaging (MRI) is recommended for further characterization. We propose contrast-enhanced ultrasound (CEUS) shows equivalent efficacy. METHODS: This prospective institutional review board approved study recruited 195 consecutive at-risk patients with a positive surveillance US. All had CEUS and MRI. Biopsy (n = 44) and follow-up are gold standard. MRI and CEUS results are classified according to liver imaging reporting and data system (LI-RADS) and patient outcome. RESULTS: As an US-based modality, CEUS is superior in confirming findings from surveillance US, correlation in 189/195 (97%) on CEUS compared to 153/195 (79%) on MRI. Within these negative MRI examinations, there are 2 hepatocellular carcinoma (HCC) and 1 cholangiocarcinoma (iCCA) diagnosed on CEUS and proven by biopsy. From 195 patients, there are 71 malignant diagnoses from all sources, including 58 LR-5 (45 on MRI and 54 on CEUS) and 13 others, including HCC outside of LR-5 category, and LR-M with biopsy proven iCCA (3 on MRI and 6 on CEUS). CEUS and MRI show concordant results in the majority of patients (146/195, 75%), including 57/146 malignant and 89/146 benign diagnoses. There are 41/57 concordant LR-5 and 6/57 concordant LR-M. When CEUS and MRI are discordant, CEUS upgraded 20 (10 biopsy-proven) from MRI LR-3/4 to CEUS LR-5 or LR-M by showing washout (WO) that MRI failed to show. Additionally, CEUS characterized time and intensity of WO and diagnosed 13/20 LR-5 by showing late and weak WO and 7 LR-M by showing fast and marked WO. CEUS is 81% sensitive and 92% specific in diagnosing malignancy. MRI is 64% sensitive and 93% specific. CONCLUSIONS: CEUS performance is at least equivalent if not superior to MRI for initial evaluation of lesions from surveillance US.

MiR-1180 from bone marrow MSCs promotes cell proliferation and glycolysis in ovarian cancer cells via SFRP1/Wnt pathway.

BACKGROUND: The ovarian cancer microenvironment is responsible for cancer cell growth and disease relapse. Bone marrow mesenchymal stem cells (BM-MSCs) play important roles in ovarian cancer, however, the mechanism of BM-MSCs inducing cell proliferation and glycolysis needs further research. METHODS: miRNA array was used to analyze the significant miRNAs. RT-qPCR was used to examine the level of miR-1180 and SFRP1. The western blotting was used to detect the protein level of SFRP1 and Wnt signal pathway. We utilized luciferase reporter assay to confirm the direct interaction of SFRP1 with miR-1180. MTT assay were employed to investigate the proliferation of ovarian cancer cells. ECAR, ATP assay were used to measure the glycolysis state of ovarian cancer cells. RESULTS: It was demonstrated that BM-MSCs promoted ovarian cancer cell proliferation and glycolysis. The miRNA profile from the BM-MSCs indicated that miR-1180 was up-regulated in the conditioned medium of BM-MSCs. MiR-1180 could accelerate ovarian cancer cell proliferation and glycolysis. We also found that up-regulation of miR-1180 activated Wnt signaling by targeting SFRP1 in ovarian cancer cells. CONCLUSION: The study demonstrated that miR-1180 was a critical miRNA mediating BM-MSCs induced cell proliferation and glycolysis and could be a new target in ovarian cancer therapy.

The circular RNA circ-ITCH suppresses ovarian carcinoma progression through targeting miR-145/RASA1 signaling.

As the leading cause of death for gynecological cancers, ovarian cancer (OC) ranks fifth overall for cancer-related death among women. Emerging evidence has indicated that circular RNA (circRNA), recognized as functional non-coding transcripts in eukaryotic cells, may be involved in many physiological or pathological processes. It was reported that circ-ITCH is downregulated in multi cancers and serves as a powerful tumor suppressor among through a competing endogenous RNA (ceRNA) pathway. However, the existence and the role of circ-ITCH in OC was not reported. Here, we found a broad down-regulation of circ-ITCH in OC tissues and cells, which correlates with a worse prognosis in OC patients. Functional studies suggest that circ-ITCH overexpression inhibits the cell viability and motility by CCK8, cell cycle, wound healing assay and invasion assay. It also inhibits the tumorigenesis ability in xenograft NOD mice in vivo. Mechanically, we demonstrated that circ-TCH acts as a ceRNA to sponge miR-145, increases the level of RASA1, and inhibits the malignant progression of OC cells via the circ-ITCH-miR-145-RASA1 axis in vitro and in vivo. Taken together, our findings provide a novel tumor suppressive role regarding circ-ITCH function in the malignant progression of OC.

Migration of Transformed Bone Marrow-Derived Cells with Peripheral Neural Tumor Traits In Vivo.

The identification of the original cells in tumors may allow for measures that protect the original cells and prevent tumor formation. In the present study, we isolated a subpopulation of cells with the features of neural tumor cells from transformed BMDCs in vitro. These neural tumor cells expressed the markers of neural tumor progenitor cells and differentiated neural tumor cells in vitro. Moreover, the subcloned cells from transformed BMDCs could migrate to distant tissues and drive peripheral neural tumors in vivo. Therefore, our results further verify that transformed mouse BMDCs are a potential source of peripheral neural tumors.

Effect of remimazolam on electroencephalogram burst suppression in elderly patients undergoing cardiac surgery: Protocol for a randomized controlled noninferiority trial.

Background: Postoperative delirium (POD) is a common complication following cardiac surgery and increases postoperative morbidity and mortality. Intraoperative electroencephalogram (EEG) burst suppression suggests excessively deep anesthesia and predicts POD. Use of remimazolam provides a stable hemodynamic status and an appropriate depth of anesthesia. We aim to assess remimazolam administered for anesthesia and sedation in elderly patients having cardiac surgery. Methods: This is a randomized controlled clinical trial with noninferiority design. A total of 260 elderly patients aged equal to or greater than 60 years undergoing cardiac surgery will be randomly allocated to receive remimazolam or propofol (1:1) for general anesthesia and postoperative sedation until extubation. The primary outcome is the cumulative time with EEG burst suppression which is obtained from the SedLine system. The noninferiority margin is 2.0 min. The secondary outcomes include the POD occurrence within the first 5 days postoperatively and the duration of perioperative hypotension. Discussion: This noninferiority trial is the first to evaluate the effect of perioperative remimazolam administration on EEG burst suppression, POD occurrence, and duration of hypotension in elderly patients who undergo cardiac surgery. Trial registration: Chinese Clinical Trial Registry (ChiCTR2200056353).

Gd-EOB-DTPA enhanced MRI based radiomics combined with clinical variables in stratifying hepatic functional reserve in HBV infected patients.

PURPOSES: To evaluate radiomics from Gd-EOB-DTPA enhanced MR combined with clinical variables for stratifying hepatic functional reserve in hepatitis B virus (HBV) patients. METHODS: Our study included 279 chronic HBV patients divided 8:2 for training and test cohorts. Radiomics features were extracted from the hepatobiliary phase (HBP) MR images. Radiomics features were selected to construct a Rad-score which was combined with clinical parameters in two models differentiating hepatitis vs. Child-Pugh A and Child-Pugh A vs. B/C. Performances of these stratifying models were compared using area under curve (AUC). RESULTS: Rad-score alone discriminated hepatitis vs. Child-Pugh A with AUC = 0.890, 0.914 and Child-Pugh A vs. B/C with AUC = 0.862, 0.865 for the training and test cohorts, respectively. Model 1 [Rad-score + clinical parameters for hepatitis vs. Child-Pugh A] showed AUC = 0.978 for the test cohort, which was higher than ALBI [albumin-bilirubin] and MELD [model for end-stage liver disease], with AUCs of 0.716, 0.799, respectively (p < 0.001, < 0.001). Model 2 [Rad-score + clinical parameters for Child-Pugh A vs. B/C] showed AUC of 0.890 in the test cohort, which was similar to ALBI (AUC = 0.908, p = 0.760), and higher than MELD (AUC = 0.709, p = 0.018). CONCLUSION: Rad-score combined with clinical variables stratifies hepatic functional reserve in HBV patients.

Intraoperative dexmedetomidine on postoperative sleep disturbance in older patients undergoing major abdominal surgery: A randomized controlled trial protocol.

Background: Postoperative sleep disturbance (PSD) occurs frequently in patients who undergo major abdominal surgical procedures. Dexmedetomidine is a promising agent to improve the quality of sleep for surgical patients. We designed this trial to investigate the effects of two different doses of intraoperative dexmedetomidine on the occurrence of PSD in elderly patients who have major abdominal surgery. Methods: In this randomized, double-blind, controlled trial, 210 elderly patients aged ≥65 years will be randomized, with an allocation ratio of 1:1:1, to two dexmedetomidine groups (intraoperative infusion of 0.3 or 0.6 µg/kg/h) and a normal saline placebo group. The primary endpoint is the occurrence of PSD on the first night after surgery, assessed using the Athens Insomnia Scale. The secondary endpoints are (1) the incidence of PSD during the 2nd, 3rd, 5th, 7th, and 30th nights postoperatively; (2) pain at rest and on movement at 24 and 48 h postoperatively, assessed using the Numerical Rating Scale; (3) the incidence of postoperative delirium during 0-7 days postoperatively or until hospital discharge, assessed using the 3-min Confusion Assessment Method; (4) depressive symptoms during 0-7 days postoperatively or until hospital discharge, assessed using the 15-items Geriatric Depression Scale; and (5) quality of recovery on postoperative days 1, 2, and 3, assessed using the 15-items Quality of Recovery Scale. Patients' sleep data will also be collected by Xiaomi Mi Band 7 for further analysis. Discussion: The findings of this trial will provide clinical evidence for improving the quality of sleep among elderly patients undergoing major abdominal surgery. Ethics and dissemination: This trial was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University (No. 2023-160). The results will be published in a peer-reviewed journal. Trial registration: Chinese Clinical Trial Registry (ChiCTR2300073163).

Association between labor epidural analgesia and gut microbiota: A prospective cohort study.

Background: Labor epidural analgesia (LEA) may influence gut microbiota. We explored the association between LEA and gut microbiota for both mothers and their newborns. Methods: In this prospective cohort study, parturients aged 25-35 years with a gestational age of 37-42 weeks and planned vaginal delivery were recruited. Twenty-one parturients received LEA (the LEA group), and 24 did not (the control group). Maternal and neonatal fecal samples were collected, and the gut microbiota profiles were analyzed using the 16S rRNA gene sequencing. The impact of LEA on gut microbiota was assessed using the general liner models. Results: We showcased the gut microbiota profile from the phyla to species levels based on data on 45 mother-newborn dyads. The results of α- and ß-diversity suggested significant changes in gut microbiota between the LEA and control groups. After adjusting for baseline confounders, the administration of LEA had positive correlations with R. ilealis (ß = 91.87, adjusted P = 0.007) in mothers; LEA also had negative correlations with A. pittii (ß = -449.36, adjusted P = 0.015), P. aeruginosa (ß = -192.55, adjusted P = 0.008), or S. maltophilia (ß = -142.62, adjusted P = 0.001) in mothers, and with Muribaculaceae (ß = -2702.77, adjusted P = 0.003) in neonates. Conclusion: LEA was associated with changes in maternal and neonatal gut microbiota, and future studies are still required to assess their impact on clinical outcomes and explore the mechanisms.

Hold Tight: Identifying Behavioral Patterns During Prolonged Work in VR Through Video Analysis.

VR devices have recently been actively promoted as tools for knowledge workers and prior work has demonstrated that VR can support some knowledge worker tasks. However, only a few studies have explored the effects of prolonged use of VR such as a study observing 16 participants working in VR and a physical environment for one work-week each and reporting mainly on subjective feedback. As a nuanced understanding of participants' behavior in VR and how it evolves over time is still missing, we report on the results from an analysis of 559 hours of video material obtained in this prior study. Among other findings, we report that (1) the frequency of actions related to adjusting the headset reduced by 46% and the frequency of actions related to supporting the headset reduced by 42% over the five days; (2) the HMD was removed 31% less frequently over the five days but for 41% longer periods; (3) wearing an HMD is disruptive to normal patterns of eating and drinking, but not to social interactions, such as talking. The combined findings in this work demonstrate the value of long-term studies of deployed VR systems and can be used to inform the design of better, more ergonomic VR systems as tools for knowledge workers.

Cdc42-interacting protein 4 is a Src substrate that regulates invadopodia and invasiveness of breast tumors by promoting MT1-MMP endocytosis.

Invadopodia are actin-rich membrane protrusions that promote extracellular matrix degradation and invasiveness of tumor cells. Src protein-tyrosine kinase is a potent inducer of invadopodia and tumor metastases. Cdc42-interacting protein 4 (CIP4) adaptor protein interacts with actin regulatory proteins and regulates endocytosis. Here, we show that CIP4 is a Src substrate that localizes to invadopodia in MDA-MB-231 breast tumor cells expressing activated Src (MDA-SrcYF). To probe the function of CIP4 in invadopodia, we established stable CIP4 knockdown in MDA-SrcYF cell lines by RNA interference. Compared with control cells, CIP4 knockdown cells degrade more extracellular matrix (ECM), have increased numbers of mature invadopodia and are more invasive through matrigel. Similar results are observed with knockdown of CIP4 in EGF-treated MDA-MB-231 cells. This inhibitory role of CIP4 is explained by our finding that CIP4 limits surface expression of transmembrane type I matrix metalloprotease (MT1-MMP), by promoting MT1-MMP internalization. Ectopic expression of CIP4 reduces ECM digestion by MDA-SrcYF cells, and this activity is enhanced by mutation of the major Src phosphorylation site in CIP4 (Y471). Overall, our results identify CIP4 as a suppressor of Src-induced invadopodia and invasion in breast tumor cells by promoting endocytosis of MT1-MMP.

Protocol for Development and Validation of Multivariable Prediction Models for Chronic Postsurgical Pain Following Video-Assisted Thoracic Surgery.

Purpose: Chronic postsurgical pain (CPSP) is a common complication after thoracic surgery and associated with long-term adverse outcomes. This study aims to develop two prediction models for CPSP after video-assisted thoracic surgery (VATS). Methods and Analysis: This single-center prospective cohort study will include a total of 500 adult patients undergoing VATS lung resection (n = 350 for development and n = 150 for external validation). Patients will be enrolled continuously at The First Affiliated Hospital of Soochow University in Suzhou, China. The cohort for external validation will be recruited in another time period. The outcome is CPSP, which is defined as pain with the numerical rating scale score of 1 or higher 3 months after VATS. Univariate and multivariable logistic regression analyses will be performed to develop two CPSP prediction models based on patients' data of postoperative day 1 and day 14, respectively. For internal validation, we will use the bootstrapping validation technique. For external validation, the discrimination capability of the models will be assessed using the area under the receiver operating characteristic curve, and the calibration will be evaluated using the calibration curve and Hosmer-Lemeshow goodness-of-fit statistic. The results will be presented in model formulas and nomograms. Conclusion: Based on the development and validation of the prediction models, our results contribute to early prediction and treatment of CPSP after VATS. Trial Registration: Chinese Clinical Trial Register (ChiCTR2200066122).

Protocol for development and validation of a prediction model for post-induction hypotension in elderly patients undergoing non-cardiac surgery: a prospective cohort study.

INTRODUCTION: Post-induction hypotension (PIH) is a common event in elderly surgical patients and is associated with increased postoperative morbidity and mortality. This study aims to develop and validate a PIH prediction model for elderly patients undergoing elective non-cardiac surgery to identify potential PIH in advance and help to take preventive measures. METHODS AND ANALYSIS: A total of 938 elderly surgical patients (n=657 for development and internal validation, n=281 for temporal validation) will be continuously recruited at The First Affiliated Hospital of Soochow University in Suzhou, China. The main outcome is PIH during the first 15 min after anaesthesia induction or before skin incision (whichever occurs first). We select candidate predictors based on published literature, professional knowledge and clinical expertise. For model development, we will use the least absolute shrinkage and selection operator regression analysis and multivariable logistic regression. For internal validation, we will apply the bootstrapping technique. After model development and internal validation, temporal validation will be conducted in patients recruited in another time period. We will use the discrimination, calibration and max-rescaled Brier score in the temporal validation cohort. Furthermore, the clinical utility of the prediction model will be assessed using the decision curve analysis, and the results will be presented in a nomogram and a web-based risk calculator. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Ethics Committee of the First Affiliated Hospital of Soochow University (Approval No. 2023-012). This PIH risk prediction model will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2200066201.

Barrier permeation and improved nanomedicine delivery in tumor microenvironments.

Nanomedicines can effectively penetrate tumor sites compared to traditionally used drugs. However, effective drugs that reach the interior of tumors remain limited. Based on studies of the complex tumor microenvironment, we summarized the barriers restricting tumor penetration of nanomedicines in this review. Penetration barriers are mainly caused by tumor blood vessels, stroma, and cell abnormalities. The repair of abnormal tumor blood vessels and tumor stroma and adjusting the physicochemical properties of nanoparticles are considered promising strategies to improve the tumor permeation of nanomedicines. The effects of nanoparticle properties, including size, shape, and surface charge, on tumor penetration were also reviewed. We expect to provide research ideas and a scientific basis for nanomedicines to increase intratumoral permeability and improve anti-tumor effects.

An Intraoperative Sub-Anesthetic Dose of Esketamine on Postoperative Depressive Symptoms in Perimenopausal Women with Breast Cancer Undergoing Modified Radical Mastectomy: Protocol for a Randomized, Triple-Blinded, Controlled Trial.

Background: Depressive symptoms are common among perimenopausal women with breast cancer having modified radical mastectomy. Esketamine exerts antidepressant effects. This study aims to assess whether an intraoperative sub-anesthetic dose of esketamine prevents postoperative depressive symptoms in these patients. Methods: In this randomized, triple-blinded, placebo-controlled trial, we will enroll 130 perimenopausal women (aged 45-60 years) with breast cancer undergoing unilateral modified radical mastectomy. Patients will be randomly assigned with a 1:1 ratio to receive either esketamine (0.25 mg/kg i.v.) or normal saline after anesthesia induction and before skin incision. The primary outcome is the incidence of depressive symptoms at day 30 postoperatively, assessed using the Beck's Depression Inventory (BDI). Secondary outcomes include incidence of depressive symptoms and BDI scores at day 1, 3, and 180 postoperatively, anxiety symptoms and scores at day 1, 3, 30, and 180 postoperatively, pain intensity and quality of recovery at day 1 and 2 postoperatively, nausea and vomiting within 48 hours postoperatively, length of postoperative hospital stay, and cancer-specific outcomes. Data will be analyzed in the modified intention-to-treat population. Discussion: This is the first trial to evaluate the effects of a sub-anesthetic dose of esketamine on depressive symptoms in perimenopausal women after modified radical mastectomy. The results of this study will help to improve their mental health and recovery after breast cancer surgery. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200064348).

BMAL1 promotes colorectal cancer cell migration and invasion through ERK- and JNK-dependent c-Myc expression.

BACKGROUND: Cancer metastasis is still a life threat to patients with colorectal cancer (CRC). Brain and muscle ARNT-like protein 1 (BMAL1) is an important biological proteins that can regulate the behavior of cancer cells and their response to chemotherapy. However, the role of BMAL1 in the tumorigenic phenotype of CRC remains unclear. Here, we aim to investigate the functional role and mechanisms of BMAL1 in CRC. METHODS: The mRNA expression of BMAL1 was studied using the Cancer Genome Atlas (TCGA) databases. The protein level in clinical tissues was confirmed by immunohistochemistry (IHC). The effects of BMAL1 on the epithelial-to-mesenchymal transition (EMT) and proliferation of CRC cell lines (including BMAL1 overexpressed or silencing cells) were studied by Transwell, wound healing, CCK-8 and colony formation experiments. A series of experiments were conducted to demonstrate the mechanisms of BMAL1 regulating EMT and cancer proliferation in vitro and in vivo. RESULTS: We found that BMAL1 expression was closely related to the poor prognosis of CRC. BMAL1 overexpression promoted cell proliferation and migration. Mechanistically, we found that BMAL1 may activate the epithelial-to-mesenchymal transition (EMT) pathway and induce the ß-catenin release further promotes the expression of oncogene c-Myc and the migration of colorectal cells by activating MAPK pathway. However, BMAL1 silencing achieved the opposite effect. In addition, blocking MAPK-signaling pathway with specific inhibitors of ERK1/2 and JNK can also downregulate the expressions of c-Myc in vitro. Taken together, these results suggested that the BMAL1/ c-Myc-signaling pathway may regulate the metastasis of CRC through the JNK/ERK1/2 MAPK-dependent pathway. CONCLUSIONS: Our study showed that BMAL1 promotes CRC metastasis through MAPK-c-Myc pathway. These results deepen our understanding of the relationship between BMAL1 and tumorigenic phenotypes, which may become a promising therapeutic target for BMAL1 overexpressing CRC.

Transducer of Cdc42-dependent actin assembly promotes epidermal growth factor-induced cell motility and invasiveness.

Toca-1 (transducer of Cdc42-dependent actin assembly) interacts with the Cdc42·N-WASP and Abi1·Rac·WAVE F-actin branching pathways that function in lamellipodia formation and cell motility. However, the potential role of Toca-1 in these processes has not been reported. Here, we show that epidermal growth factor (EGF) induces Toca-1 localization to lamellipodia, where it co-localizes with F-actin and Arp2/3 complex in A431 epidermoid carcinoma cells. EGF also induces tyrosine phosphorylation of Toca-1 and interactions with N-WASP and Abi1. Stable knockdown of Toca-1 expression by RNA interference has no effect on cell growth, EGF receptor expression, or internalization. However, Toca-1 knockdown cells display defects in EGF-induced filopodia and lamellipodial protrusions compared with control cells. Further analyses reveal a role for Toca-1 in localization of Arp2/3 and Abi1 to lamellipodia. Toca-1 knockdown cells also display a significant defect in EGF-induced motility and invasiveness. Taken together, these results implicate Toca-1 in coordinating actin assembly within filopodia and lamellipodia to promote EGF-induced cell migration and invasion.

Nickel-Catalyzed Chemo- and Regioselective Arylcyanation of ß,γ-Unsaturated Amides.

A nickel-catalyzed intermolecular arylcyanation of 8-aminoquinolinyl ß,γ-unsaturated amides is reported. The three-component reaction directly afforded diverse ß-cyano γ-aryl amides with exclusive chemo- and regioselectivity. The synthetic practicality of this approach is further demonstrated through multigram scale reaction, expanded transformations of the nitrile product, late-stage modification of complex molecules, and direct drug synthesis.

Quantifying the Effects of Working in VR for One Week.

Virtual Reality (VR) provides new possibilities for modern knowledge work. However, the potential advantages of virtual work environments can only be used if it is feasible to work in them for an extended period of time. Until now, there are limited studies of long-term effects when working in VR. This paper addresses the need for understanding such long-term effects. Specifically, we report on a comparative study $i$, in which participants were working in VR for an entire week-for five days, eight hours each day-as well as in a baseline physical desktop environment. This study aims to quantify the effects of exchanging a desktop-based work environment with a VR-based environment. Hence, during this study, we do not present the participants with the best possible VR system but rather a setup delivering a comparable experience to working in the physical desktop environment. The study reveals that, as expected, VR results in significantly worse ratings across most measures. Among other results, we found concerning levels of simulator sickness, below average usability ratings and two participants dropped out on the first day using VR, due to migraine, nausea and anxiety. Nevertheless, there is some indication that participants gradually overcame negative first impressions and initial discomfort. Overall, this study helps lay the groundwork for subsequent research, by clearly highlighting current shortcomings and identifying opportunities for improving the experience of working in VR.

SFRP4+ stromal cell subpopulation with IGF1 signaling in human endometrial regeneration.

Our understanding of full-thickness endometrial regeneration after injury is limited by an incomplete molecular characterization of the cell populations responsible for the organ functions. To help fill this knowledge gap, we characterized 10,551 cells of full-thickness normal human uterine from two menstrual phases (proliferative and secretory phase) using unbiased single cell RNA-sequencing. We dissected cell heterogeneity of main cell types (epithelial, stromal, endothelial, and immune cells) of the full thickness uterine tissues, cell population architectures of human uterus cells across the menstrual cycle. We identified an SFRP4+ stromal cell subpopulation that was highly enriched in the regenerative stage of the human endometria during the menstrual cycle, and the SFRP4+ stromal cells could significantly enhance the proliferation of human endometrial epithelial organoid in vitro, and promote the regeneration of endometrial epithelial glands and full-thickness endometrial injury through IGF1 signaling pathway in vivo. Our cell atlas of full-thickness uterine tissues revealed the cellular heterogeneities, cell population architectures, and their cell-cell communications during the monthly regeneration of the human endometria, which provide insight into the biology of human endometrial regeneration and the development of regenerative medicine treatments against endometrial damage and intrauterine adhesion.