Spatiotemporal evolution and mechanisms of tourism efficiency and its decomposition: Evidence from 63 counties in Zhejiang, China.

Although efficiency analysis could reflect the state and quality of tourism's economic development, no research has been conducted investigating the spatiotemporal evolution and mechanisms of county-level tourism efficiency. We quantified tourism efficiency and its decomposition in 63 counties of Zhejiang, employing the bootstrap data envelopment analysis (DEA), hot spot analysis, and quantile regression to explore the spatiotemporal evolution and influencing factors of tourism efficiency, and examine its driving and constraining mechanisms. The results uncovered obvious upward trends in the tourism efficiency of Zhejiang's counties, with the mean value increasing from 0.285 to 0.688. Compared with scale efficiency, the influence of technological efficiency on the growth of comprehensive efficiency increased remarkably. Significant differences were evident in the spatial distributions of the identified hot and cold spots of comprehensive efficiency, which were respectively distributed in northern and southern Zhejiang. The distributions of decomposition efficiency were found to be spatially dependent. The driving mechanism of tourism efficiency involve two driving influences and two constraining influences, including economy and resource driving, market and traffic driving, industry and traffic constraining, and market and industry constraining. The findings of this study contribute to understanding of tourism efficiency growth in regional destinations and provide insights for strategic policymaking in various counties of Zhejiang.

Promoting leisure functions through setting creative linguistic landscapes in recreational zones.

Using creativity to promote recreational services is crucial. Accordingly, creative linguistic landscapes (CLLs) are being used to improve visitors' experiences in some recreational zones. However, relevant research is still in its early stages. Therefore, this study was conducted. It summarized the leisure function categories and function evaluation indicators of CLLs in recreational zones respectively based on image materials and related online reviews. The leisure function outcomes of all CLL types were ranked using the fuzzy PROMETHEE method; based on this ranking, a CLL configuration optimization mode was suggested. The findings reveal the following. (1) Currently, there are mainly nine leisure function types of CLL in practice, although the type structure is severely imbalanced; there are 12 primary corresponding function evaluation indicators, although each of them draws significantly different attention. (2) There are notable variations among the outcomes of different types of functions of CLL: mood adjustment is the most advantageous function of CLL for leisure services, followed by emotional guidance and cognitive building functions; (3) According to the study findings, in the configuration of CLL, which aims at leisure function optimization, the "function focusing and coordinating mode (the superior functions of CLL are focused on and its various functions are coordinated)" should be adopted. The results provide meaningful lessons for the establishment of rational and effective CLL in recreational zones.

Fe doping enhanced Cr(VI) adsorption efficiency of cerium-based adsorbents: Adsorption behaviors and inner removal mechanisms.

Cerium-based adsorbents possessed unique advantages of valence variability and abundant oxygen vacancies in hexavalent chromium (Cr(VI)) adsorption, but high cost and unstable properties restricted their application in Cr(VI) contained wastewater treatment. Herein, a series of bimetallic adsorbents with different cerium/iron ratios (CeFe@C) were prepared by adding inexpensive Fe into Ce-based adsorbents (Ce@C), and the effect of Fe doping on adsorption properties of Ce@C for Cr(VI) was investigated thoroughly. Compared with pristine Ce@C, CeFe@C exhibited excellent removal performance for Cr(VI), and the improved maximum adsorption capacity reached 75.11 mg/g at 25℃. Benefiting from Fe doping, CeFe@C had good regeneration property, with only 25 % decrease after five adsorption-desorption cycles. Contents of trivalent cerium (Ce(III)) and oxygen vacancies (Ov) in bimetallic adsorbents were positively correlated with divalent iron (Fe(II)) doping, indicating that the formation of Ce(III) and surface defects on Ce@C could be effectively regulated by Fe doping. Density functional theory (DFT) calculation results further proved that the doped Fe enhanced the electron transfer effectively and lowered the energy barriers of Cr(VI) adsorption onto Ce@C surface, strengthening the reduction and complexation to Cr(VI). This study provides new insights for improving the Cr(VI) removal performance by modified Ce-based adsorbents, and further promotes the utilization potentiality of low-cost and low-toxicity Ce-based adsorbents in Cr(VI)-containing wastewater treatment.

Intubation at Birth Is Associated with Death after Pulmonary Hemorrhage in Very Low Birth Weight Infants.

OBJECTIVE: This retrospective cohort study was performed to clarify the association between intubation in the delivery room and the mortality after pulmonary hemorrhage in very low birth weight infants (VLBWIs) during hospitalization. METHODS: The study participants were screened from the VLBWIs admitted to the neonatal intensive care unit (NICU) of the Children's Hospital Affiliated to Nanjing Medical University from 31 July 2019 to 31 July 2022. The newborns who ultimately were included were those infants who survived until pulmonary hemorrhage was diagnosed. These subjects were divided into the intubation-at-birth group (n = 29) and the non-intubation-at-birth group (n = 35), retrospectively. RESULTS: Univariate analysis found that the intubation group had a higher mortality and shorter hospital stay than the non-intubation group (p < 0.05) (for mortality: 25/29 (86.21%) in intubation group versus 14/35 (40.00%) in non-intubation group). By multivariate analysis, the result further showed that intubation in the delivery room was related to shorter survival time and higher risk of death (adjusted hazard ratio: 2.341, 95% confidence interval: 1.094-5.009). CONCLUSIONS: Intubation at birth suggested a higher mortality in the VLBWIs when pulmonary hemorrhage occurred in the NICU.

Comparison of genes involved in brain development: insights into the organization and evolution of the telencephalic pallium.

The mechanisms underlying the organization and evolution of the telencephalic pallium are not yet clear.. To address this issue, we first performed comparative analysis of genes critical for the development of the pallium (Emx1/2 and Pax6) and subpallium (Dlx2 and Nkx1/2) among 500 vertebrate species. We found that these genes have no obvious variations in chromosomal duplication/loss, gene locus synteny or Darwinian selection. However, there is an additional fragment of approximately 20 amino acids in mammalian Emx1 and a poly-(Ala)6-7 in Emx2. Lentiviruses expressing mouse or chick Emx2 (m-Emx2 or c-Emx2 Lv) were injected into the ventricle of the chick telencephalon at embryonic Day 3 (E3), and the embryos were allowed to develop to E12-14 or to posthatchling. After transfection with m-Emx2 Lv, the cells expressing Reelin, Vimentin or GABA increased, and neurogenesis of calbindin cells changed towards the mammalian inside-out pattern in the dorsal pallium and mesopallium. In addition, a behavior test for posthatched chicks indicated that the passive avoidance ratio increased significantly. The study suggests that the acquisition of an additional fragment in mammalian Emx2 is associated with the organization and evolution of the mammalian pallium.

Link between mutations in ACVRL1 and PLA2G4A genes and chronic intestinal ulcers: A case report and review of literature.

BACKGROUND: Genetic factors of chronic intestinal ulcers are increasingly garnering attention. We present a case of chronic intestinal ulcers and bleeding associated with mutations of the activin A receptor type II-like 1 (ACVRL1) and phospholipase A2 group IVA (PLA2G4A) genes and review the available relevant literature. CASE SUMMARY: A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain, diarrhea, and dark stools. At the onset 6 years ago, the patient had received treatment at a local hospital for abdominal pain persisting for 7 d, under the diagnosis of diffuse peritonitis, acute gangrenous appendicitis with perforation, adhesive intestinal obstruction, and pelvic abscess. The surgical treatment included exploratory laparotomy, appendectomy, intestinal adhesiolysis, and pelvic abscess removal. The patient's condition improved and he was discharged. However, the recurrent episodes of abdominal pain and passage of black stools started again one year after discharge. On the basis of these features and results of subsequent colonoscopy, the clinical diagnosis was established as inflammatory bowel disease (IBD). Accordingly, aminosalicylic acid, immunotherapy, and related symptomatic treatment were administered, but the symptoms of the patient did not improve significantly. Further investigations revealed mutations in the ACVRL1 and PLA2G4A genes. ACVRL1 and PLA2G4A are involved in angiogenesis and coagulation, respectively. This suggests that the chronic intestinal ulcers and bleeding in this case may be linked to mutations in the ACVRL1 and PLA2G4A genes. Oral Kangfuxin liquid was administered to promote healing of the intestinal mucosa and effectively manage clinical symptoms. CONCLUSION: Mutations in the ACVRL1 and PLA2G4A genes may be one of the causes of chronic intestinal ulcers and bleeding in IBD. Orally administered Kangfuxin liquid may have therapeutic potential.

Risk of candidiasis associated with interleukin-17 inhibitors: Implications and management.

The application of interleukin-17 (IL-17) inhibitors, including secukinumab, ixekizumab, brodalumab, and bimekizumab, are associated with elevated risk of candidiasis. These medications interfere with the IL-17 pathway, which is essential for maintaining mucosal barriers and coordinating the immune response against Candida species. The observational data and clinical trials demonstrate the increased incidence of candidiasis in individuals treated with IL-17 inhibitors. Brodalumab and bimekizumab pose a greater risk than secukinumab in eliciting candidiasis, whereas the data regarding ixekizumab are equivocal. Higher doses and prolonged treatment duration of IL-17 inhibitors increase the risk of candidiasis by compromising the immune response against Candida species. Prior to prescribing IL-17 inhibitors, healthcare professionals should comprehensively evaluate patients' medical histories and assess their risk factors. Patients should be educated on the signs and symptoms of candidiasis to facilitate early detection and intervention. Future research should focus on identifying the risk factors associated with candidiasis in patients receiving IL-17 inhibitors. Prospective studies and long-term surveillance are required to explore the impact of specific inhibitors on the incidence and severity of candidiasis and to evaluate the effectiveness of combination therapies, such as concurrent use of IL-17 inhibitors and prophylactic antifungal agents.

Interleukin inhibitors and the associated risk of candidiasis.

Interleukins (ILs) are vital in regulating the immune system, enabling to combat fungal diseases like candidiasis effectively. Their inhibition may cause enhanced susceptibility to infection. IL inhibitors have been employed to control autoimmune diseases and inhibitors of IL-17 and IL-23, for example, have been associated with an elevated risk of Candida infection. Thus, applying IL inhibitors might impact an individual's susceptibility to Candida infections. Variations in the severity of Candida infections have been observed between individuals with different IL inhibitors, necessitating careful consideration of their specific risk profiles. IL-1 inhibitors (anakinra, canakinumab, and rilonacept), IL-2 inhibitors (daclizumab, and basiliximab), and IL-4 inhibitors (dupilumab) have rarely been associated with Candida infection. In contrast, tocilizumab, an inhibitor of IL-6, has demonstrated an elevated risk in the context of coronavirus disease 2019 (COVID-19) treatment, as evidenced by a 6.9% prevalence of candidemia among patients using the drug. Furthermore, the incidence of Candida infections appeared to be higher in patients exposed to IL-17 inhibitors than in those exposed to IL-23 inhibitors. Therefore, healthcare practitioners must maintain awareness of the risk of candidiasis associated with using of IL inhibitors before prescribing them. Future prospective studies need to exhaustively investigate candidiasis and its associated risk factors in patients receiving IL inhibitors. Implementing enduring surveillance methods is crucial to ensure IL inhibitors safe and efficient utilization of in clinical settings.

ATG-101 Is a Tetravalent PD-L1×4-1BB Bispecific Antibody That Stimulates Antitumor Immunity through PD-L1 Blockade and PD-L1-Directed 4-1BB Activation.

Immune checkpoint inhibitors (ICI) have transformed cancer treatment. However, only a minority of patients achieve a profound response. Many patients are innately resistant while others acquire resistance to ICIs. Furthermore, hepatotoxicity and suboptimal efficacy have hampered the clinical development of agonists of 4-1BB, a promising immune-stimulating target. To effectively target 4-1BB and treat diseases resistant to ICIs, we engineered ATG-101, a tetravalent "2+2″ PD-L1×4-1BB bispecific antibody. ATG-101 bound PD-L1 and 4-1BB concurrently, with a greater affinity for PD-L1, and potently activated 4-1BB+ T cells when cross-linked with PD-L1-positive cells. ATG-101 activated exhausted T cells upon PD-L1 binding, indicating a possible role in reversing T-cell dysfunction. ATG-101 displayed potent antitumor activity in numerous in vivo tumor models, including those resistant or refractory to ICIs. ATG-101 greatly increased the proliferation of CD8+ T cells, the infiltration of effector memory T cells, and the ratio of CD8+ T/regulatory T cells in the tumor microenvironment (TME), rendering an immunologically "cold" tumor "hot." Comprehensive characterization of the TME after ATG-101 treatment using single-cell RNA sequencing further revealed an altered immune landscape that reflected increased antitumor immunity. ATG-101 was well tolerated and did not induce hepatotoxicity in non-human primates. According to computational semimechanistic pharmacology modeling, 4-1BB/ATG-101/PD-L1 trimer formation and PD-L1 receptor occupancy were both maximized at around 2 mg/kg of ATG-101, providing guidance regarding the optimal biological dose for clinical trials. In summary, by localizing to PD-L1-rich microenvironments and activating 4-1BB+ immune cells in a PD-L1 cross-linking-dependent manner, ATG-101 safely inhibits growth of ICI resistant and refractory tumors. SIGNIFICANCE: The tetravalent PD-L1×4-1BB bispecific antibody ATG-101 activates 4-1BB+ T cells in a PD-L1 cross-linking-dependent manner, minimizing the hepatotoxicity of existing 4-1BB agonists and suppressing growth of ICI-resistant tumors. See related commentary by Ha et al., p. 1546.

Investigating Structural Relationships between Professional Identity, Learning Engagement, Academic Self-Efficacy, and University Support: Evidence from Tourism Students in China.

In order to foster students' development and enhance the training quality within tourism programs at universities, this study aims to investigate the relationships among tourism students' professional identity, academic self-efficacy, learning engagement, and university support. Professional identity refers to learners' recognition and understanding of their study programs and is viewed as a dynamic, progressive process consisting of professional cognition, professional emotion, and professional appraisal. Data were collected from 333 tourism students studying at Chinese universities. They were analyzed through SPSS and SmartPLS. The results revealed that there is no significant correlation between students' professional cognition and learning engagement. However, students' professional emotions and professional appraisals positively influence learning engagement. Moreover, all three dimensions of professional identity exhibit positive effects on students' academic self-efficacy. Additionally, students' academic self-efficacy demonstrates a positive impact on learning engagement, and university support is associated with increased learning engagement and academic self-efficacy. This study contributes to a comprehensive understanding of the learning experience of tourism students and aims to facilitate the advancement of tourism education through cultivating students' professional identity towards tourism and developing students' career commitment in the tourism industry. Theoretical and practical implications are discussed.