The digital economy enables high-quality cultural tourism integration:mechanisms, channels, and empirical evidence

Following the rapid scientific and technological development in this new era of global industrial transformation, the tourism industry has overcome the severe challenges of the COVID-19 pandemic by taking advantage of new development opportunities. Digital technologies, such as big data, cloud computing, artificial intelligence, and fifth-generation mobile communications have released the huge potential for promoting the development of the high-quality cultural tourism integration. Scholars have explored the benefits of developing and improving the quality of cultural tourism integration in addition to how the digital economy can promote the development of cultural tourism integration. Most existing research has regarded the digital economy as a means to promote the development of cultural tourism integration;however, there is relatively little systematic research on the logical mechanism, transmission channels, and practical paths that enable the high-quality development of cultural tourism integration. Therefore, this paper systematically explores the logical mechanism, direct effects, and transmission mechanisms in the digital economy that promote the development of high-quality cultural tourism integration. The study findings open up the "black box"of developing high-quality cultural tourism integration and help to establish its scientific basis in the digital economy. Based on a systematic explanation of how the digital economy enables the high-quality development and transmission of cultural tourism integration through organizational, technological, and product innovation channels, this paper conducts empirical testing using 2011-2020 panel data from 30 Chinese provinces (excluding Tibet, Hong Kong, Macao, and Taiwan of Chian) and obtains three main findings. First, the digital economy has a positive enabling effect on the development of high-quality cultural tourism integration, which has been verified in benchmark regression, instrumental variable regression, and robustness testing. Second, this enabling effect shows regional differences. For example, East China benefits from its relatively well-developed digital economy and can enjoy the dividends from its high-quality cultural tourism destinations. However, although West China has seen rapid growth in its digital economy, the region also shows a trend of increasing marginal effects from its enabling effect, while the digital economy's enabling trend in Central China still needs to be strengthened. Third, by constructing a transmission channel, that is, "digital economy-organization-technology-product innovation-developmental quality of cultural tourism integration", we find that the digital economy can positively promote the development of high-quality cultural tourism integration by regulating transmission channels for innovation, such as organizational, technological, and product innovation. According to the research conclusions, measures to promote the development of high-quality cultural tourism integration in the digital economy should be taken in the following four areas. First, local governments and cultural tourism departments should deepen their development strategies to integrate the digital economy with the real economy and systematically cultivate new drivers for the development of high-quality cultural tourism integration. Second, a digital cultural tourism platform should be built to optimize the value creation mechanism for the development of high-quality cultural tourism integration. Third, regional heterogeneity characteristics should be combined with the digital economy's enabling effect to implement a differentiated digital cultural tourism development strategy. Fourth, organizational, technological, and product innovation advantages should be cultivated to expand the transmission channels for the development of high-quality cultural tourism integration within the digital economy.

Nirmatrelvir/ritonavir use in patients with COVID-19 on hemodialysis: a case series

Patients undergoing hemodialysis (HD) are particularly vulnerable to coronavirus disease 2019 (COVID-19) and are at increased risk of developing severe infection. However, given the exclusion of such patients from clinical trials, there are limited data regarding the effectiveness of the antiviral drug nirmatrelvir/ritonavir (N/R) in patients on HD. We prescribed N/R to four patients on HD with COVID-19 after obtaining informed consent. Their clinical symptoms were improved at approximately 3 days after N/R administration. The viral load was reduced after approximately 10 days. The main adverse effects were nausea and vomiting. Rational dosage adjustment obtained good tolerance but did not influence the efficacy. These results suggest that N/R may be a promising agent for patients on HD with COVID-19.

A SARS-CoV-2-specific CAR-T-cell model identifies felodipine, fasudil, imatinib, and caspofungin as potential treatments for lethal COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019 (COVID-19) severity and lethality. However, drugs that are effective against inflammation to treat lethal COVID-19 are still urgently needed. Here, we constructed a SARS-CoV-2 spike protein-specific CAR, and human T cells infected with this CAR (SARS-CoV-2-S CAR-T) and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients, causing cytokine storm and displaying a distinct memory, exhausted, and regulatory T-cell phenotype. THP1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in coculture. Based on this "two-cell" (CAR-T and THP1 cells) model, we screened an FDA-approved drug library and found that felodipine, fasudil, imatinib, and caspofungin were effective in suppressing the release of cytokines, which was likely due to their ability to suppress the NF-κB pathway in vitro. Felodipine, fasudil, imatinib, and caspofungin were further demonstrated, although to different extents, to attenuate lethal inflammation, ameliorate severe pneumonia, and prevent mortality in a SARS-CoV-2-infected Syrian hamster model, which were also linked to their suppressive role in inflammation. In summary, we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput manner. The drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe, inexpensive, and easily accessible for immediate use in most countries.

Adjustment of Immunosuppressants to Facilitate Anti-COVID-19 Antibody Production after mRNA Vaccination in Liver Transplant Recipients.

Liver transplant recipients are immunocompromised and have low immunogenicity to produce antibodies in anti-COVID-19 vaccination. Whether immunosuppressant adjustment could facilitate anti-COVID-19 antibody production in anti-COVID-19 mRNA vaccination is undetermined. Our patients were informed to temporarily suspend mycophenolate mofetil (MMF) or everolimus (EVR) for 2 weeks during both the 1st and 2nd doses of Moderna mRNA-1273 vaccine. A total of 183 recipients receiving two doses of Moderna mRNA-1273 vaccine were enrolled and grouped into tacrolimus monotherapy (MT, n = 41), and dual therapy with non-adjustment (NA, n = 23), single suspension (SS, n = 19) and double suspension (DS, n = 100) of MMF/EVR in two-dose mRNA vaccination. A total of 155 (84.7%) patients had a humoral response to vaccines in this study. The humoral response rates were 60.9%, 89.5%, 91.0% and 80.5% in NA, SS, DS, and MT group patients, respectively (p = 0.003). Multivariate analysis showed that favorable factors for humoral response were temporary suspension of MMF/EVR and monotherapy, and unfavorable factors were deceased donor liver transplantation, WBC count < 4000/uL, lymphocyte < 20% and tacrolimus trough level ≥ 6.8 ng/mL. In conclusion, temporary two-week suspension of anti-proliferation immunosuppressants could create a window to facilitate antibody production during anti-COVID-19 mRNA vaccination. This concept may be applied to other vaccinations in liver transplant recipients.

The effects of comorbidities on the change of taste and smell in COVID-19 patients.

Background: Sudden chemosensory changes were considered an early predictor of COVID-19. Here, the effects of comorbidities on changes in taste and smell in COVID-19 patients were investigated based on a worldwide study. Methods: Data analyzed here were collected from the Global Consortium for Chemosensory Research (GCCR) core questionnaire, including questions regarding preexisting disease conditions. Overall, the final sample of 12,438 participants who were diagnosed with COVID-19 included patients with preexisting conditions. Mixed linear regression models were used to test our hypothesis, and the p-value of interaction was examined. Results: A total of 61,067 participants completed the GCCR questionnaire, including 16,016 participants had preexisting diseases. The multivariate regression analysis showed that individuals with high blood pressure, lung disease, or sinus problems, or neurological diseases exhibited worse self-reported smell loss (p < .05), but no apparent significant differences in the smell or taste recovery. COVID-19 patients with seasonal allergy/hay fever lost their olfactory ability more than patients who did not have it (with 11.90 [9.67, 14.13] vs. without 6.97 [6.04, 7.91], p < .0001). The taste ability, smell loss and taste loss after COVID-19 recovery also decreased in the COVID-19 patients with seasonal allergy/hay fever (p < .001). Preexisting condition of diabetes did not worsen to chemosensory disorder but also had no obvious impact on the chemosensory recovery after acute infection. Preexisting diseases also affected the type of smell change in the COVID-19 patients with seasonal allergy/hay fever or sinus problems (p < .05). Conclusions: COVID-19 patients with high blood pressure, lung disease, or sinus problems, or neurological diseases exhibited worse self-reported smell loss, but no differences in the smell or taste recovery. COVID-19 patients with seasonal allergy/hay fever had greater loss of smell and taste, poorer smell and taste recovery. Level of Evidence: 4.

Determinants of Antibody Response to SARS-CoV-2 Vaccines in Liver Transplant Recipients: The Role of Immunosuppression Reduction.

Liver transplant recipients on chronic immunosuppression show an attenuated antibody response after SARS-CoV-2 vaccination. Adjusting immunosuppressants during vaccination remains debated. We enrolled 380 liver transplant recipients receiving 2 doses of a protein subunit, mRNA, or a vector vaccine. The patients were informed to temporarily suspend immunosuppression for 2 weeks for both vaccination doses. We measured anti-live-SARS-CoV-2 spike neutralizing antibody levels at 1-2 months after the second vaccination; 83.9% of patients had humoral responses (SARS-CoV-2 NT50 ≥ 9.62 IU/mL) to 2 doses of vaccines. The mRNA (86.7%) and protein subunit vaccines (85%) yielded higher response rates than the vector vaccines (40.9%). Immunosuppression suspension during the two vaccinations yielded a higher response rate (91.5% vs. 57.7%). Only eight patients (2.1%) experienced transaminase level elevation of thrice the normal value (>110 IU/L) after the second vaccination. Most recovered spontaneously after resuming immunosuppression. Multivariate analysis revealed ABO incompatibility, white blood cell count <4000, lymphocyte count <20%, tacrolimus trough level >6.5 ng/mL, and no immunosuppression adjustment as independent risk factors to nonresponse. The mRNA and protein subunit vaccines yielded a higher response rate. Immunosuppression suspension for 2 weeks enhanced the antibody response. ABO incompatibility, leukopenia, lymphopenia, a high tacrolimus trough level, and no immunosuppression adjustment are associated with nonresponse.

Bibliometric analysis of top-cited articles in Journal of Dental Sciences.

Background/purpose: Bibliometric analysis is a method for quantifying the article distribution, impact, and performance. The purpose of this study was to identify the most top-cited articles published in Journal of Dental Sciences (JDS) and further analyze their main characteristics. Materials and methods: Web of Science, Journal Citation Reports database was searched to retrieve the most-cited articles in JDS published from 2007 to July 31, 2022. Among the included top-cited articles, the following parameters were recorded and analyzed: article title, article type, year, country, number of citations, and average citations pre year. Microsoft Excel was applied for the descriptive bibliometric analysis. Results: 41 top-cited articles were filtered from total 1165 JDS articles in Web of Science database. The results showed that 41 top-cited articles were cited between 20 and 186 times from Journal Citation Reports. Most of the article types are original article (28/41, 68.29%) following by review article (7/41, 17.07%). The majority of articles were originated from Taiwan (23/41, 56.10%). The top 4 most cited articles were relative to the research topic on COVID-19, lateral canal, guided-tissue regeneration barriers, and platelet-rich fibrin, respectively. However, articles analyzed by the average citations per year since publication were focused on COVID-19 followed by artificial intelligence. Conclusion: This bibliometric analysis illustrates the progress and trend of researches in JDS. The results may also offer a reference for recognizing the hot issues with the most citations in JDS.

In-Silico Selection of Aptamer Targeting SARS-CoV-2 Spike Protein.

Aptamers are single-stranded, short DNA or RNA oligonucleotides that can specifically bind to various target molecules. To diagnose the infected cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in time, numerous conventional methods are applied for viral detection via the amplification and quantification of DNA or antibodies specific to antigens on the virus. Herein, we generated a large number of mutated aptamer sequences, derived from a known sequence of receptor-binding domain (RBD)-1C aptamer, specific to the RBD of SARS-CoV-2 spike protein (S protein). Structural similarity, molecular docking, and molecular dynamics (MD) were utilized to screen aptamers and characterize the detailed interactions between the selected aptamers and the S protein. We identified two mutated aptamers, namely, RBD-1CM1 and RBD-1CM2, which presented better docking results against the S protein compared with the RBD-1C aptamer. Through the MD simulation, we further confirmed that the RBD-1CM1 aptamer can form the most stable complex with the S protein based on the number of hydrogen bonds formed between the two biomolecules. Based on the experimental data of quartz crystal microbalance (QCM), the RBD-1CM1 aptamer could produce larger signals in mass change and exhibit an improved binding affinity to the S protein. Therefore, the RBD-1CM1 aptamer, which was selected from 1431 mutants, was the best potential candidate for the detection of SARS-CoV-2. The RBD-1CM1 aptamer can be an alternative biological element for the development of SARS-CoV-2 diagnostic testing.

A map of bat virus receptors derived from single-cell multiomics.

Bats are considered reservoirs of many lethal zoonotic viruses and have been implicated in several outbreaks of emerging infectious diseases, such as SARS-CoV, MERS-CoV, and SARS-CoV-2. It is necessary to systematically derive the expression patterns of bat virus receptors and their regulatory features for future research into bat-borne viruses and the prediction and prevention of pandemics. Here, we performed single-nucleus RNA sequencing (snRNA-seq) and single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq) of major organ samples collected from Chinese horseshoe bats (Rhinolophus affinis) and systematically checked the expression pattern of bat-related virus receptors and chromatin accessibility across organs and cell types, providing a valuable dataset for studying the nature of infection among bat-borne viruses.

In-Silico Selection of Aptamer Targeting SARS-CoV-2 Spike Protein

Aptamers are single-stranded, short DNA or RNA oligonucleotides that can specifically bind to various target molecules. To diagnose the infected cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in time, numerous conventional methods are applied for viral detection via the amplification and quantification of DNA or antibodies specific to antigens on the virus. Herein, we generated a large number of mutated aptamer sequences, derived from a known sequence of receptor-binding domain (RBD)-1C aptamer, specific to the RBD of SARS-CoV-2 spike protein (S protein). Structural similarity, molecular docking, and molecular dynamics (MD) were utilized to screen aptamers and characterize the detailed interactions between the selected aptamers and the S protein. We identified two mutated aptamers, namely, RBD-1CM1 and RBD-1CM2, which presented better docking results against the S protein compared with the RBD-1C aptamer. Through the MD simulation, we further confirmed that the RBD-1CM1 aptamer can form the most stable complex with the S protein based on the number of hydrogen bonds formed between the two biomolecules. Based on the experimental data of quartz crystal microbalance (QCM), the RBD-1CM1 aptamer could produce larger signals in mass change and exhibit an improved binding affinity to the S protein. Therefore, the RBD-1CM1 aptamer, which was selected from 1431 mutants, was the best potential candidate for the detection of SARS-CoV-2. The RBD-1CM1 aptamer can be an alternative biological element for the development of SARS-CoV-2 diagnostic testing.

Non-invasive transdermal delivery of biomacromolecules with fluorocarbon-modified chitosan for melanoma immunotherapy and transdermal vaccines (preprint)

Transdermal drug delivery has been regarded as an alternative to oral delivery and subcutaneous injection for its non-invasiveness, improved patient compliance and avoidance of the first-pass effect. However, needleless transdermal delivery of biomacromolecules remains a challenge. Herein, a transdermal delivery platform is developed to achieve highly efficient non-invasive transdermal delivery of biomacromolecules. In this system, fluorocarbon modified chitosan (FCS) is optimized as an effective yet biocompatible transdermal carrier to assemble with different proteins including immune checkpoint blockade (ICB) antibodies, and antigens such as the spike (S) protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The formed FCS-containing nanocomplexes exhibited rather effective transdermal penetration ability via both intercellular and transappendageal routes. Interestingly, non-invasive transdermal delivery of ICB antibodies by FCS induced stronger immune responses to treat mouse melanoma compared to intravenous injection of free antibodies, while presenting reduced systemic toxicity. Moreover, transdermal delivery of SARS-CoV-2 vaccine using FCS-containing nanocomplexes resulted in comparable humoral immunity as well as improved cell immunity and immune memory compared to that achieved with subcutaneous vaccine injection. Thus, FCS-based transdermal delivery systems may provide a compelling opportunity to overcome the skin barrier for efficient transdermal delivery of biomacromolecules, widening the range of therapeutics that can be topically administered.

Sequencing on an imported case in China of COVID-19 Delta variant emerging from India in a cargo ship in Zhoushan, China.

A cluster of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections was found in a cargo ship under repair in Zhoushan, China. Twelve of 20 crew members were identified as SARS-CoV-2 positive. We analyzed four sequences and identified them all in the Delta branch emerging from India with 7-8 amino acid mutation sites in the spike protein.

The clinical implication of gamma-glutamyl transpeptidase in COVID-19.

BACKGROUND AND AIM: Coronavirus disease 2019 (COVID-19) is a life-threatening disease that predominantly causes respiratory failure. The impact of COVID-19 on other organs remains elusive. Herein, we aimed to investigate the effects of COVID-19 on the hepatobiliary system. METHODS: In the current study, we obtained the clinical records and laboratory results from 66 laboratory-confirmed patients with COVID-19 at the Wuhan Tongji Hospital between 10 February 2020 and 28 February 2020. The detailed clinical features and laboratory findings were collected for analysis. Bioinformatics analysis was conducted to evaluate the correlation between gamma-glutamyl transferase (GGT) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry receptor angiotensin-converting enzyme 2 (ACE2). RESULTS: In this cohort, 30 (51.7%) patients had abnormal liver function on admission, which was associated with disease severity and enriched in the male and diabetic patients. The elevated levels of direct bilirubin (P = 0.029) and GGT (P = 0.004) were common in patients with severe pneumonia when compared with those with mild pneumonia. In addition, elevated levels of GGT (P = 0.003) and aspartate aminotransferase (AST) (P = 0.007) were positively associated with longer hospital stay. The expression of ACE2 was closely associated with GGT in various human tissues because they shared the common transcriptional regulator hepatic nuclear factor-1ß (HNF1B). CONCLUSIONS: Increased GGT levels were common in severe cases and elevated GGT levels were positively associated with prolonged hospital stay and disease severity. Due to the consistent expression with ACE2, GGT is a potent biomarker indicating the susceptibility of SARS-CoV-2 infection.

Initiating narrative medicine into dental education: Opportunity, change, and challenge.

Recently, the patient-centered and comprehensive dental treatment are emphasized as the same important competency as traditional clinical skill training in dental education. It is a silver lining to reorganize current dental education and redefine the role of dentistry to dentist, patient, and society. Narrative medicine has emerged as a variant from medical humanities and takes inspiration from philosophy, literature, poetry, art, ethics, and social sciences. Narrative medicine adds humanistic care with empathy and listening to patients in daily care. In this article, we introduce the definition of narrative medicine, the concept of narrative dentistry, implementation of narrative medicine into dental education, and challenges in initiating narrative dentistry. During the current COVID-19 pandemic, it also affords the opportunity to initiate narrative medicine into dental education, dentist could emerge to heal patient holistically, but not simply eliminate oral diseases.

Characteristics of asymptomatic COVID-19 infection and progression: A multicenter, retrospective study.

Novel coronavirus disease 2019 (COVID-19), caused by novel coronavirus SARS-CoV-2, has spread globally since the end of 2019. Asymptomatic carriers are of great concern as they can undermine the interventions to stop the pandemic. However, there is limited information about the characteristics and outcomes of the asymptomatic patients. Therefore, we conducted this retrospective study and retrieved data of 79 asymptomatic COVID-19 patients at admission from three designated hospitals in Wuhan, China. The asymptomatic patients could happen at any age, ranged from 9 to 96 years. These patients also had lower levels of alanine aminotransferase and C-reactive protein. Patchy shadowing was the most common manifestation in computed tomography scan. Some asymptomatic carriers developed mild or moderate symptoms during hospitalization. Age and comorbidities, especially hypertension, may be predictive factors for symptom development in the initially asymptomatic carriers at admission. Early detection and treatment for these presymptomatic patients before symptom onset can shorten the communicable period for the coronavirus and reduce the occurrence of severe cases.