Large-scale across species transcriptomic analysis identifies genetic selection signatures associated with longevity in mammals.

Lifespan varies significantly among mammals, with more than 100-fold difference between the shortest and longest living species. This natural difference may uncover the evolutionary forces and molecular features that define longevity. To understand the relationship between gene expression variation and longevity, we conducted a comparative transcriptomics analysis of liver, kidney, and brain tissues of 103 mammalian species. We found that few genes exhibit common expression patterns with longevity in the three organs analyzed. However, pathways related to translation fidelity, such as nonsense-mediated decay and eukaryotic translation elongation, correlated with longevity across mammals. Analyses of selection pressure found that selection intensity related to the direction of longevity-correlated genes is inconsistent across organs. Furthermore, expression of methionine restriction-related genes correlated with longevity and was under strong selection in long-lived mammals, suggesting that a common strategy is utilized by natural selection and artificial intervention to control lifespan. Our results indicate that lifespan regulation via gene expression is driven through polygenic and indirect natural selection.

Comparative time-series multi-omics analyses suggest H1.2 involvement in anoxic adaptation and cancer resistance.

The naked mole rat (NMR), Heterocephalus glaber, is known as the longest-lived rodent and is extraordinarily resistant to hypoxia and cancer. Here, both NMR embryonic fibroblasts (NEFs) and their mouse counterparts (MEFs) were subjected to anoxic conditions (0% O2, 5% CO2). A combination of comparative transcriptomics and proteomics was then employed to identify differentially expressed genes (DEGs). Notably, we observed distinct levels of histone H1.2 (encoded by HIST1H1C) accumulation between NEFs and MEFs. Subsequent mechanistic analyses showed that higher H1.2 expression in NEFs was associated with the lower expression of its inhibitor, PARP1. Additionally, we discovered that H1.2 can directly interact with HIF-1α PAS domains, thereby promoting the expression of HIF-1α through facilitating the dimerization with HIF-1ß. The overexpression of H1.2 was also found to trigger autophagy and to suppress the migration of cancer cells, as well as the formation of xenograft tumors, via the NRF2/P62 signaling pathway. Moreover, an engineered H1.2 knock-in mouse model exhibited significantly extended survival in hypoxic conditions (4% O2) and showed a reduced rate of tumor formation. Collectively, our results indicate a potential mechanistic link between H1.2 and the dual phenomena of anoxic adaptation and cancer resistance.

Phylogenomics Reveals High Levels of Incomplete Lineage Sorting at the Ancestral Nodes of the Macaque Radiation.

The genus Macaca includes 23 species assigned into 4 to 7 groups. It exhibits the largest geographic range and represents the most successful example of adaptive radiation of nonhuman primates. However, intrageneric phylogenetic relationships among species remain controversial and have not been resolved so far. In this study, we conducted a phylogenomic analysis on 16 newly generated and 8 published macaque genomes. We found strong evidence supporting the division of this genus into 7 species groups. Incomplete lineage sorting (ILS) was the primary factor contributing to the discordance observed among gene trees; however, we also found evidence of hybridization events, specifically between the ancestral arctoides/sinica and silenus/nigra lineages that resulted in the hybrid formation of the fascicularis/mulatta group. Combined with fossil data, our phylogenomic data were used to establish a scenario for macaque radiation. These findings provide insights into ILS and potential ancient introgression events that were involved in the radiation of macaques, which will lead to a better understanding of the rapid speciation occurring in nonhuman primates.

Phylogenomics of Afrotherian mammals and improved resolution of extant Paenungulata.

Molecular investigations have gathered a diverse set of mammals-predominantly African natives like elephants, hyraxes, and aardvarks-into a clade known as Afrotheria. Nevertheless, the precise phylogenetic relationships among these species remain contentious. Here, we sourced orthologous markers and ultraconserved elements to discern the interordinal connections among Afrotherian mammals. Our phylogenetic analyses bolster the common origin of Afroinsectiphilia and Paenungulata, and propose Afrosoricida as the closer relative to Macroscelidea rather than Tubulidentata, while also challenging the notion of Sirenia and Hyracoidea as sister taxa. The approximately unbiased test and the gene concordance factor uniformly recognized the alliance of Proboscidea with Hyracoidea as the dominant topology within Paenungulata. Investigation into sites with extremly high phylogenetic signal unveiled their potential to intensify conflicts in the Paenungulata topology. Subsequent exploration suggested that incomplete lineage sorting was predominantly responsible for the observed contentious relationships, whereas introgression exerted a subsidiary influence. The divergence times estimated in our study hint at the Cretaceous-Paleogene (K-Pg) extinction event as a catalyst for Afrotherian diversification. Overall, our findings deliver a tentative but insightful overview of Afrotheria phylogeny and divergence, elucidating these relationships through the lens of phylogenomics.

Accuracy and Consistency of 3-Dimensional Magnetic Resonance Imaging Is Comparable With 3-Dimensional Computed Tomography in Assessing Glenohumeral Instability: A Systematic Review.

PURPOSE: To compare the accuracy of 3-dimensional (3D) magnetic resonance imaging (MRI) with that of 3D computed tomography (CT) in evaluating glenoid bone loss (GBL). METHODS: This review aligned with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed, the Cochrane Library, Embase, and Web of Science were obtained from data inception to August 28, 2023. The search term "glenoid bone loss" was extracted and analyzed via stringent inclusion and exclusion criteria. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 combined with the QUADAS-Comparative to assess the heterogeneity of included studies. RESULTS: A total of 1,589 related studies were retrieved, and 10 studies were finally included, of which a total of 143 shoulders were evaluated. The index test in QUADAS-Comparative was low risk in 9 studies. 3D MRI measurements of GBL were primarily best-fit circles (n = 9). In both clinical and cadaveric studies, the mean percentages of GBL measured by 3D MRI were 0.38% to 2.19% and 0.25% to 6.1% when compared with 3D CT and standard reference values, respectively. Intraclass correlation coefficient agreement greater than 0.9 between GBL percentages measured by 3D CT and 3D MRI. 3D MRI also could accurately measure glenoid width, glenoid height, humeral head width, and height. 3D MRI reconstruction time was similar to that of 3D CT, which was mainly 10 to 15 minutes. CONCLUSIONS: In both clinical and cadaveric studies, compared with 3D CT, 3D MRI is accurate and consistent in assessing glenohumeral bone, especially in measuring GBL, and the reconstruction time of 3D MRI is similar to 3D CT. LEVEL OF EVIDENCE: Level Ⅲ, systematic review of Level Ⅱ-Ⅲ studies.

Outcomes from different aspects indicate the all-inside technique may serve as an ideal option for anterior cruciate ligament reconstruction.

PURPOSE: To evaluate the postoperative outcomes of the all-inside technique in arthroscopic anterior cruciate ligament reconstruction (ACLR). METHODS: Patients who underwent ACLR using the all-inside technique between 2018 and 2021 were retrospectively assessed. All patients were followed up for at least 2 years. Functional recovery and pain relief were assessed using the International Knee Documentation Committee (IKDC) score, Lysholm score, Knee Injury and Osteoarthritis Outcome Score (KOOS) and visual analogue scale (VAS). Instrumented laxity was assessed via side-to-side difference using the Kneelax3 arthrometer. Graft maturity was estimated using the signal-to-noise quotient value based on magnetic resonance imaging (MRI). Adverse events during and after the surgery were recorded. RESULTS: A total of 78 patients were included in this study, with a mean age of 28.1 ± 7.6 years. The IKDC (p < 0.001), Lysholm (p < 0.001) and KOOS (p < 0.001 for all subgroups) scores at the final follow-up were significantly higher than those before the surgery. The VAS scores (p < 0.05) were significantly lower than those before surgery. The side-to-side difference results indicated that 50 patients had a difference of less than 3 mm, indicating a tight graft, whereas only 1 patient had a difference of >5 mm, indicating a loose graft. The median signal-to-noise quotient of the graft on MRI was 1.4 (P25, P75: 1.0, 2.0). No intraoperative adverse events were observed. Postoperative adverse events included three cases of infection, three cases of graft rerupture, two cases of cyclops lesion and one case of surgical intervention for a meniscal tear. CONCLUSION: ACLR using the all-inside technique offers promising results in patients with ACL rupture. LEVEL OF EVIDENCE: Level IV.

A randomized controlled trial comparison of PTEBL and traditional teaching methods in "Stop the Bleed" training.

BACKGROUND: The Stop the Bleed (STB) training program was launched by the White House to minimize hemorrhagic deaths. Few studies focused on the STB were reported outside the United States. This study aimed to evaluate the effectiveness of a problem-, team- and evidence-based learning (PTEBL) approach to teaching, compared to traditional teaching methods currently employed in STB courses in China. METHODS: This study was a parallel group, unmasked, randomised controlled trial. We included third-year medical students of a five-year training program from the Xiangya School of Medicine, Central South University who voluntarily participated in the trial. One hundred fifty-three medical students were randomized (1:1) into the PTEBL group (n = 77) or traditional group (n = 76). Every group was led by a single instructor. The instructor in the PTEBL group has experienced in educational reform. However, the instructor in the traditional group follows a traditional teaching mode. The teaching courses for both student groups had the same duration of four hours. Questionnaires were conducted to assess teaching quality before and after the course. The trial was registered in the Central South University (No. 2021JY188). RESULTS: In the PTEBL group, students reported mastery in three fundamental STB skills-Direct Finger Compression (61/77, 79.2%), Packing (72/77, 93.8%), and Tourniquet Placement (71/77, 92.2%) respectively, while 76.3% (58/76), 89.5% (68/76), and 88.2% (67/76) of students in the traditional group (P > 0.05 for each pairwise comparison). 96.1% (74/77) of students in the PTEBL group felt prepared to help in an emergency, while 90.8% (69/76) of students in the traditional group (P > 0.05). 94.8% (73/77) of students reported improved teamwork skills after the PTEBL course, in contrast with 81.6% (62/76) of students in the traditional course (P = 0.011). Furthermore, a positive correlation was observed between improved clinical thinking skills and improved teamwork skills (R = 0.82, 95% CI: 0.74-0.88; P < 0.001). CONCLUSIONS: Compared with the traditional teaching method, the PTEBL method was superior in teaching teamwork skills, and has equally effectively taught hemostasis techniques in the emergency setting. The PTEBL method can be introduced to the STB training in China.

The impact of evidence-based nursing leadership in healthcare settings: a mixed methods systematic review.

BACKGROUND: The central component in impactful healthcare decisions is evidence. Understanding how nurse leaders use evidence in their own managerial decision making is still limited. This mixed methods systematic review aimed to examine how evidence is used to solve leadership problems and to describe the measured and perceived effects of evidence-based leadership on nurse leaders and their performance, organizational, and clinical outcomes. METHODS: We included articles using any type of research design. We referred nurses, nurse managers or other nursing staff working in a healthcare context when they attempt to influence the behavior of individuals or a group in an organization using an evidence-based approach. Seven databases were searched until 11 November 2021. JBI Critical Appraisal Checklist for Quasi-experimental studies, JBI Critical Appraisal Checklist for Case Series, Mixed Methods Appraisal Tool were used to evaluate the Risk of bias in quasi-experimental studies, case series, mixed methods studies, respectively. The JBI approach to mixed methods systematic reviews was followed, and a parallel-results convergent approach to synthesis and integration was adopted. RESULTS: Thirty-one publications were eligible for the analysis: case series (n = 27), mixed methods studies (n = 3) and quasi-experimental studies (n = 1). All studies were included regardless of methodological quality. Leadership problems were related to the implementation of knowledge into practice, the quality of nursing care and the resource availability. Organizational data was used in 27 studies to understand leadership problems, scientific evidence from literature was sought in 26 studies, and stakeholders' views were explored in 24 studies. Perceived and measured effects of evidence-based leadership focused on nurses' performance, organizational outcomes, and clinical outcomes. Economic data were not available. CONCLUSIONS: This is the first systematic review to examine how evidence is used to solve leadership problems and to describe its measured and perceived effects from different sites. Although a variety of perceptions and effects were identified on nurses' performance as well as on organizational and clinical outcomes, available knowledge concerning evidence-based leadership is currently insufficient. Therefore, more high-quality research and clinical trial designs are still needed. TRAIL REGISTRATION: The study was registered (PROSPERO CRD42021259624).

Influencing factors and risk prediction model for cervical cancer recurrence. / å®«é¢ˆç™Œå¤å‘çš„å½±å“å› ç´ åŠé£Žé™©é¢„æµ‹æ¨¡åž‹.

OBJECTIVES: Cervical cancer is the most common malignant tumor in the female reproductive system worldwide. The recurrence rate for the treated cervical cancer patients is high, which seriously threatens women's lives and health. At present, the risk prediction study of cervical cancer has not been reported. Based on the influencing factors of cervical cancer recurrence, we aim to establish a risk prediction model of cervical cancer recurrence to provide a scientific basis for the prevention and treatment of cervical cancer recurrence. METHODS: A total of 4 358 cervical cancer patients admitted to the Hunan Cancer Hospital from January 1992 to December 2005 were selected as research subjects, and the recurrence of cervical cancer patients after treatment was followed up. Univariate analysis was used to analyze the possible influencing factors. Variables that were significant in univariate analysis or those that were not significant in univariate analysis but may be considered significant were included in multivariate Cox regression analysis to establish a cervical cancer recurrence risk prediction model. Line graphs was used to show the model and it was evaluated by using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis. RESULTS: Univariate analysis showed that the recurrence rates of cervical cancer patients with different age, age of menarche, parity, miscarriage, clinical stage, and treatment method were significantly different (all P<0.05). Multivariate Cox regression analysis showed that RR=-0.489×(age≥55 years old)+0.481×(age at menarche >15 years old)+0.459×(number of miscarriages≥3)+0.416×(clinical stage II)+0.613×(clinical stage III/IV)+0.366×(the treatment method was surgery + chemotherapy) + 0.015×(the treatment method was chemotherapy alone). The area under the ROC curve (AUC) of the Cox risk prediction model for cervical cancer recurrence constructed was 0.736 (95% CI 0.684 to 0.789), the best prediction threshold was 0.857, the sensitivity was 0.576, and the specificity was 0.810. The accuracy of the Cox risk model constructed by this model was good. From the clinical decision curve, the net benefit value was high and the validity was good. CONCLUSIONS: Patient age, age at menarche, miscarriages, clinical stages, and treatment methods are independent factors affecting cervical cancer recurrence. The Cox proportional hazards prediction model for cervical cancer recurrence constructed in this study can be better used for predicting the risk of cervical cancer recurrence.

The Application of a Moldable Skin Barrier in the Self-Care of Elderly Ostomy Patients.

The quality of ostomy directly affects the stoma patient's quality of life. This study investigated the application of a moldable skin barrier in the self-care of elderly stoma patients after colostomy for colorectal cancer. A total of 104 elderly stoma patients (65-79 years) who underwent colostomy because of colorectal cancer were randomly divided into an experimental group (56 cases) receiving a moldable skin barrier and a control group (48 cases) receiving a conventional skin barrier. The information on peristomal irritant dermatitis occurrence, the satisfaction of self-care, and related care costs were collected 1 month after patients were discharged from the hospital. The overall incidence of irritant dermatitis was significantly lower (p = .01), the self-care satisfaction score was significantly higher (p = .02), and the cost for leakage-proof cream (p < .001) was significantly lower in the experimental group than in the control group. In contrast, no significant differences in the cost of ostomy equipment and the barrier replacement interval were observed. In conclusion, a moldable skin barrier can reduce the incidence of irritant dermatitis in elderly stoma patients, improve their self-care satisfaction, and reduce the cost of leakage-proof cream use compared with the conventional stoma skin barrier.

Application of Complete Decongestive Therapy in Patients with Secondary Bilateral Lower Limb Lymphedema after Comprehensive Treatment of Gynecological Malignant Tumor.

Objective: The purpose of this study is to investigate the effect of complete decongestive therapy (CDT), based on fluoroscopy-guided manual lymph drainage (FG-MLD), combined with intermittent pneumatic compression (IPC) on patients with secondary bilateral lower limb lymphedema after comprehensive treatment for gynecological malignant tumors. Methods: After comprehensive treatment for gynecological malignant tumors, 18 patients suffering from bilateral lower limb lymphedema were evaluated and treated by specialist nurses (with the qualification of lymphedema therapists). The treatment course included manual drainage, IPC, bandaging, functional exercise, and skincare etc., which are performed once a day for a total of 18 times. Results: After performing the treatment 18 times, a significant reduction is observed in the patient's bilateral lower limb circumference, extracellular water (ECW) content, and lower limb segment ECW ratio. Moreover, the 50-kHz bioelectrical impedance and quality of life (QoL) scores are found to be significantly higher than before treatment (all p < 0.05). Subjective symptoms also improve significantly (p < 0.05), except for local swelling (p = 0.289 > 0.05). Conclusions: CDT based on FG-MLD, combined with IPC, effectively relieves secondary bilateral lower limb lymphedema after comprehensive treatment of gynecological malignant tumors. It also improves subjective symptoms and patients' QoL, thus deserving clinical reference and promotion.

Predicting lower limb lymphedema after cervical cancer surgery using artificial neural network and decision tree models.

PURPOSE: This study aimed to develop and validate accessible artificial neural network and decision tree models to predict the risk of lower limb lymphedema after cervical cancer surgery. METHODS: We selected 759 patients who underwent cervical cancer surgery at the Hunan Cancer Hospital from January 2010 to January 2020, collecting demographic, behavioral, clinicopathological, and disease-related data. The artificial neural network and decision tree techniques were used to construct prediction models for lower limb lymphedema after cervical cancer surgery. Then, the models' predictive efficacies were evaluated to select the optimal model using several methods, such as the area under the receiver operating characteristic curve and accuracy, sensitivity, and specificity tests. RESULTS: In the training set, the artificial neural network and decision tree model accuracies for predicting lower limb lymphedema after cervical cancer surgery were 99.80% and 88.14%, and the sensitivities 99.50% and 74.01%, respectively; the specificities were 100% and 95.20%, respectively. The area under the receiver operating characteristic curve was 1.00 for the artificial neural network and 0.92 for the decision tree model. In the test set, the artificial neural network and decision tree models' accuracies were 86.70% and 82.02%, and the sensitivities 65.70% and 67.11%, respectively; the specificities were 96.00% and 89.47%, respectively. CONCLUSION: Both models had good predictive efficacy for lower limb lymphedema after cervical cancer surgery. However, the predictive performance and stability were superior in the artificial neural network model than in the decision tree model.

A Mobile Instant Messaging-Delivered Psychoeducational Intervention for Cancer Caregivers: A Randomized Clinical Trial.

Importance: Psychoeducational interventions (PEIs), which provide both information and emotional and psychosocial support, may address the unmet needs of the caregivers of adolescent and young adult patients with cancer. Objective: To explore the effects of an instant messaging-delivered PEI on anxiety, depression, quality of life (QOL), and coping and determine whether the intervention reduces caregivers' unmet needs. Design, Setting, and Participants: This randomized clinical trial using an intention-to-treat protocol was conducted from April 1 to September 14, 2022, in a tertiary cancer hospital in China and included caregivers of patients diagnosed with cancer at age 15 to 39 years recruited using convenience sampling. Intervention: Caregivers were allocated 1:1 using a randomized block scheme to the intervention or control group. The intervention group received a 5-week PEI and usual care, whereas the control group received only usual care. The PEI was delivered through articles and calls through an instant messaging application. Main Outcomes and Measures: The primary outcomes were changes in the levels of caregivers' anxiety and depression, measured using the 7-Item Generalized Anxiety Disorder Scale and the Patient Health Questionnaire 9, respectively. The secondary outcomes were changes in the levels of caregivers' QOL, coping, and unmet needs. Results: Of the 160 participants, 92 (57.5%) were male; mean (SD) age was 40.27 (8.33) years. Compared with the control group, the intervention group had significantly greater reduction in severity of anxiety (B = -3.231; 95% CI, -4.746 to -1.716; P < .001) and depression (B = -3.253; 95% CI, -5.052 to -1.454; P < .001), smaller reduction in QOL (B = 13.574; 95% CI, 0.488-26.661; P = .04), and greater reduction in unmet needs (B = -12.136; 95% CI, -18.307 to -5.965; P < .001) after the intervention. Twelve weeks after baseline, the intervention group demonstrated a significantly greater reduction only in severity of anxiety (B = -1.890; 95% CI, -3.382 to -0.397; P = .01). Conclusions and Relevance: In this randomized clinical trial of a mobile instant messaging-delivered PEI, caregivers' unmet needs, anxiety, and depression decreased significantly and QOL declined at a significantly slower rate immediately after the intervention in the intervention group compared with the control group. A sustained effect on anxiety was observed 12 weeks after baseline. Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR2200055951.

Evolutionary origin of the chordate nervous system revealed by amphioxus developmental trajectories.

The common ancestor of all vertebrates had a highly sophisticated nervous system, but questions remain about the evolution of vertebrate neural cell types. The amphioxus, a chordate that diverged before the origin of vertebrates, can inform vertebrate evolution. Here we develop and analyse a single-cell RNA-sequencing dataset from seven amphioxus embryo stages to understand chordate cell type evolution and to study vertebrate neural cell type origins. We identified many new amphioxus cell types, including homologues to the vertebrate hypothalamus and neurohypophysis, rooting the evolutionary origin of these structures. On the basis of ancestor-descendant reconstruction of cell trajectories of the amphioxus and other species, we inferred expression dynamics of transcription factor genes throughout embryogenesis and identified three ancient developmental routes forming chordate neurons. We characterized cell specification at the mechanistic level and generated mutant lines to examine the function of five key transcription factors involved in neural specification. Our results show three developmental origins for the vertebrate nervous system: an anterior FoxQ2-dependent mechanism that is deeply conserved in invertebrates, a less-conserved route leading to more posterior neurons in the vertebrate spinal cord and a mechanism for specifying neuromesoderm progenitors that is restricted to chordates. The evolution of neuromesoderm progenitors may have led to a dramatic shift in posterior neural and mesodermal cell fate decisions and the body elongation process in a stem chordate.

Factors Influencing Lower Limb Lymphedema After Cervical Cancer Surgery: A Case-Control Study.

Background: To analyze the factors influencing lower limb lymphedema (LLL) after cervical cancer surgery and provide a scientific reference for its effective prevention and control. Methods and Results: Patients at a tertiary tumor hospital between January 2010 and January 2020 who received surgical treatment for cervical cancer were included in this study. Patients were divided into lymphedema case group (n = 253) and control group (n = 506) according to lymphedema occurrence, and univariate and multivariate analyses were used to analyze the factors influencing the occurrence of LLL after cervical cancer surgery. Multifactor conditional logistic regression analysis revealed that risk factors for lymphedema occurrence included body mass index, level of education, the presence of preoperative radiotherapy and chemotherapy, radiotherapy within 3 months after postoperative chemoradiotherapy, emergence of coronary heart disease within 3 months, vaginal disease, occurrence of postoperative complications, cervical cancer diagnosis before the manifestation of menstrual abnormalities, and a history of previous surgery. Conclusion: Postoperative LLL after cervical cancer surgery is a chronic progressive disease, and no cure for LLL has been identified. Thus, determining the risk factors associated with LLL occurrence after uterine and cervical cancer surgery and the development of targeted prevention and early intervention strategies is urgently needed.

The Feasibility and Acceptability of a Needs-Oriented Psychoeducational Intervention Among Caregivers of Adolescent and Young Adult Cancer Patients: A Pilot Randomized Controlled Trial.

BACKGROUND: Little is known about the psychoeducational interventions for caregivers of adolescent and young adult (AYA) cancer patients. OBJECTIVE: To evaluate the feasibility and acceptability of a needs-oriented psychoeducational intervention among caregivers of AYA cancer patients. METHODS: In this 2-arm (parallel-group), pilot randomized controlled trial, participants were randomized to the intervention or control group. Participants in the control group received usual care, whereas those in the intervention group received a needs-oriented psychoeducational intervention via WeChat as well as the usual care. Feasibility was evaluated on recruitment, attrition, and adherence rates and the data collection process. Acceptability was assessed based on participants' satisfaction with and perceived usefulness of the intervention, collected using a questionnaire. In addition, a semistructured interview was conducted to explore their experiences. RESULTS: Twenty-four caregivers of AYA cancer patients were recruited, with a consent rate of 61.5%. The attrition and response rates 5 weeks after baseline were 8.3% and 91.7%. Among the 12 participants in the intervention group, 10 (83.3%) completed all of the 5 weekly sessions. Most of the participants were satisfied with the program and perceived its usefulness. The semistructured interviews revealed 3 major categories: facilitators of participation, perception of the intervention, and perceived benefits. CONCLUSIONS: The needs-oriented psychoeducational intervention delivered through WeChat is feasible for and acceptable to caregivers of AYA cancer patients. A full-scale study is warranted to examine the effects of this intervention on caregivers' health outcomes. IMPLICATIONS FOR PRACTICE: The WeChat-based, needs-oriented psychoeducational intervention may be beneficial to improve caregivers' health outcomes.

Insights into the Notch signaling pathway in degenerative musculoskeletal disorders: Mechanisms and perspectives.

Degenerative musculoskeletal disorders are a group of age-related diseases of the locomotive system that severely affects the patient's ability to work and cause adverse sequalae such as fractures and even death. The incidence and prevalence of degenerative musculoskeletal disorders is rising owing to the aging of the world's population. The Notch signaling pathway, which is expressed in almost all organ systems, extensively regulates cell proliferation and differentiation as well as cellular fate. Notch signaling shows increased activity in degenerative musculoskeletal disorders and retards the progression of degeneration to some extent. The review focuses on four major degenerative musculoskeletal disorders (osteoarthritis, intervertebral disc degeneration, osteoporosis, and sarcopenia) and summarizes the pathophysiological functions of Notch signaling in these disorders, especially its role in stem/progenitor cells in each disorder. Finally, a conclusion will be presented to explore the research and application of the perspectives on Notch signaling in degenerative musculoskeletal disorders.

Comparative susceptibility of SARS-CoV-2, SARS-CoV, and MERS-CoV across mammals.

Exploring wild reservoirs of pathogenic viruses is critical for their long-term control and for predicting future pandemic scenarios. Here, a comparative in vitro infection analysis was first performed on 83 cell cultures derived from 55 mammalian species using pseudotyped viruses bearing S proteins from SARS-CoV-2, SARS-CoV, and MERS-CoV. Cell cultures from Thomas's horseshoe bats, king horseshoe bats, green monkeys, and ferrets were found to be highly susceptible to SARS-CoV-2, SARS-CoV, and MERS-CoV pseudotyped viruses. Moreover, five variants (del69-70, D80Y, S98F, T572I, and Q675H), that beside spike receptor-binding domain can significantly alter the host tropism of SARS-CoV-2. An examination of phylogenetic signals of transduction rates revealed that closely related taxa generally have similar susceptibility to MERS-CoV but not to SARS-CoV and SARS-CoV-2 pseudotyped viruses. Additionally, we discovered that the expression of 95 genes, e.g., PZDK1 and APOBEC3, were commonly associated with the transduction rates of SARS-CoV, MERS-CoV, and SARS-CoV-2 pseudotyped viruses. This study provides basic documentation of the susceptibility, variants, and molecules that underlie the cross-species transmission of these coronaviruses.

Correlated evolution of social organization and lifespan in mammals.

Discerning the relationship between sociality and longevity would permit a deeper understanding of how animal life history evolved. Here, we perform a phylogenetic comparative analysis of ~1000 mammalian species on three states of social organization (solitary, pair-living, and group-living) and longevity. We show that group-living species generally live longer than solitary species, and that the transition rate from a short-lived state to a long-lived state is higher in group-living than non-group-living species, altogether supporting the correlated evolution of social organization and longevity. The comparative brain transcriptomes of 94 mammalian species identify 31 genes, hormones and immunity-related pathways broadly involved in the association between social organization and longevity. Further selection features reveal twenty overlapping pathways under selection for both social organization and longevity. These results underscore a molecular basis for the influence of the social organization on longevity.

Chromosome-level Asian elephant genome assembly and comparative genomics of long-lived mammals reveal the common substitutions for cancer resistance.

The naked mole rat (Heterocephalus glaber), bats (e.g., genus Myotis), and elephants (family Elephantidae) are known as long-lived mammals and are assumed to be excellent cancer antagonists. However, whether there are common genetic changes underpinning cancer resistance in these long-lived species is yet to be fully established. Here, we newly generated a high-quality chromosome-level Asian elephant (Elephas maximus) genome and identified that the expanded gene families in elephants are involved in Ras-associated and base excision repair pathways. Moreover, we performed comparative genomic analyses of 12 mammals and examined genes with signatures of positive selection in elephants, naked mole rat, and greater horseshoe bat. Residues at positively selected sites of CDR2L and ALDH6A1 in these long-lived mammals enhanced the inhibition of tumor cell migration compared to those in short-lived relatives. Overall, our study provides a new genome resource and a preliminary survey of common genetic changes in long-lived mammals.