Exosomes may be the carrier of acupuncture treatment for major depressive disorder.

The incidence of major depressive disorder (MDD) is increasing all over the world. There is a great need for complementary or alternative therapies with high safety, few side effects, and precise efficacy to care for MDD. In China, acupuncture has significant laboratory data and clinical trials to demonstrate its antidepressant efficacy. However, there is no clear answer as to how it works. Exosomes are membranous vesicles that rely on cellular multivesicular bodies (MVBs) fused to the cell membrane for release into the extracellular matrix. Almost all cell types are capable of producing and releasing exosomes. As a result, exosomes contain complex RNAs and proteins from their relatives (Cells that secretes exosomes). They can cross biological barriers and participate in biological activities, such as cell migration, angiogenesis, and immune regulation. These properties have made them a popular research topic. Some experts have suggested that exosomes may serve as delivery vehicles for acupuncture to work. This presents both an opportunity and a new challenge for improving the protocols of acupuncture as a treatment for MDD. To better define the relationship between MDD, exosomes, and acupuncture, we reviewed the literature from the last few years. Inclusion criteria included randomized controlled trials and basic trials evaluating acupuncture in the treatment or prevention of MDD, the role of exosomes in the development and progression of MDD, and the role of exosomes in acupuncture. We believe that acupuncture may affect the distribution of exosomes in vivo, and exosomes may be a new carrier for acupuncture treatment of MDD in the future.

Overcoming Pharmaceutical Bottlenecks for Nucleic Acid Drug Development.

The outbreak of the coronavirus disease 2019 (COVID-19) pandemic and swift approval of two mRNA vaccines have put nucleic acid therapeutics in the spotlight of both the scientific community and the general public. Actually, in addition to mRNAs, multiple nucleic acid therapeutics have been successively commercialized over the past few years. The rapid development of nucleic acid drugs not only demonstrates their superior potency but also marks a new era of the field. Compared with conventional treatments targeting proteins rather than the root causes of diseases at the genetic level, nucleic acids are capable of achieving long-standing or even curative effects against undruggable disorders by modulating gene expression via inhibition, editing, addition, or replacement. This offers a terrific arsenal for expanding therapeutic access to diseases lacking current treatment options and developing vaccines to provide swift responses to emerging global health threats.Despite the stunning success and recent resurgence of interest in the field, the unfavorable physicochemical characteristics (i.e., the negative charge, large molecular weight, and hydrophilicity), susceptibility to nuclease degradation, off-target toxicity, and immunogenicity are a brake for moving nucleic acid therapeutics from bench to bedside. Currently, developing technologies to improve the circulation stability, targeting affinity, cellular entry, endolysosomal escape, efficacy, and safety of nucleic acid drugs still remains a major pharmaceutical bottleneck.In this Account, we outline the research efforts from our group on the development of technology platforms to overcome the pharmaceutical bottlenecks for nucleic acid therapeutics. We have engineered a variety of intelligent delivery platforms such as synthetic nanomaterials (i.e., lipid nanoparticles, polymers, and inorganic nanoparticles), physical delivery methods (i.e., electroporation), and naturally derived vehicles (i.e., extracellular vesicles), aiming at endowing nucleic acids with improved circulation stability, targeting affinity, and cellular internalization (Get in) and stimuli responsive endolysosomal escape capability (Get out). Moreover, we will discuss our progress in developing a series of modification strategies for sequence engineering of nucleic acids to endow them with enhanced nuclease resistance, translation efficiency, and potency while alleviating their off-target toxicity and immunogenicity (Sequence engineering). Integrating these technologies may promote the development of nucleic acid therapeutics with potent efficacy and improved safety (Efficacy & safety). With this Account, we hope to offer insights into rational design of cutting-edge nucleic acid therapeutic platforms. We believe that the continuing advances in nucleic acid technologies together with academic-industry collaborations in the clinic, will promise to usher in more clinically translatable nucleic acid therapeutics in the foreseeable future.

Psychological Distress and Physical Adverse Events of COVID-19 Vaccination among Healthcare Workers in Taiwan.

The COVID-19 pandemic places high pressure on everyone, including healthcare workers (HCWs), thus causing them to experience psychological distress. HCWs have priority in receiving the COVID-19 vaccine. However, few studies have identified adverse events (AEs) and psychological distress in the HCWs group. Therefore, we investigated the association between psychological distress and AEs and the determinants of protective behaviors in Taiwanese HCWs. A longitudinal measurement was conducted among HCWs at National Cheng Kung University Hospital (NCKUH), Tainan, Taiwan (n = 483, mean age = 37.55 years). All HCWs completed an online questionnaire on psychological distress, COVID-19 vaccination AEs, and protective behaviors. We used generalized estimating equations (GEE) to analyze the correlation between psychological distress and AEs, and used multivariable logistic regressions to explore the predictors of protective behaviors. Depression and distress and anger were significantly associated with various physical AEs (p = 0.045 to p < 0.001). Suicidal thoughts became a significant independent variable of systemic AEs after COVID-19 vaccination (p = 0.014 to p < 0.001). People of older ages or females engaged more in washing their hands, wearing masks, and reducing their presence in crowded places. Suicidal thoughts were related to the occurrence of systemic AEs among HCWs. Doctors performed better at preventive behaviors compared to nurses and other HCWs. HCWs who experienced anxiety and nervousness tended to avoid crowds.

Factors associated with insomnia and suicidal thoughts among outpatients, healthcare workers, and the general population in Taiwan during COVID-19 pandemic: a cross-sectional study.

BACKGROUND: Insomnia and suicidal thoughts are two of the negative impacts that have been caused by the COVID-19 pandemic. Identifying the factors that contribute to these psychological problems may help develop strategies to sustain the mental health of the public. The present study examined the psychosocial impacts caused by the COVID-19 pandemic among different populations in Taiwan, and investigated the relationships between these psychosocial variables, insomnia, and suicidal thoughts. METHODS: Between September 2020 and May 2021, online questionnaires including psychometrically validated scales were distributed to a convenience sample of outpatients (n = 205), healthcare workers (HCWs) (n = 500), and individuals in the general population (n = 1200) in Taiwan to collect data regarding their insomnia severity, suicidal thoughts, fear of COVID-19, trust of information, and resilience. Multivariate logistic regression methods were used to identify variables associated with suicidal thoughts and insomnia. RESULTS: Greater fear of COVID-19 was significantly associated with suicidal thoughts: odds ratios (ORs) with 95% confidence interval (CI) = 1.155 (1.002-1.330) for outpatients; 1.127 (1.035-1.228) for HCWs; and 1.100 (1.130-1.222) for those in the general population. Higher resilience was significantly associated with lower insomnia: OR (95% CI) = 0.819 (0.725-0.926) for outpatients; 0.803 (0.728-0.887), for HCWs; 0.829 (0.785-0.875), and for those in the general population. In addition, there was a statistically significant association between insomnia diagnosis and greater fear of COVID-19 among HCWs (OR [95% CI] = 1.102 [1.062-1.144]) and those in the general population (OR [95% CI] = 1.079 [1.053-1.106]). Among outpatients, there was a statistically significant association between suicidal thoughts and lower trust of information (OR [95% CI] = 0.794 [0.646-0.976]), while among those in the general population there was a statistically significant association between suicidal thoughts and higher insomnia severity (OR [95% CI] = 1.175 [1.13-1.222]). A statistically significant association was also found between insomnia diagnosis and higher suicidal thoughts among those in the general population (OR [95% CI] = 3.455 [2.338-5.106]). CONCLUSIONS: Trust of information, fear, and resilience were important factors for suppressing suicidal thoughts and insomnia among the three study populations. Health policies that monitor psychological status and build resiliency of the public are recommended to help develop tailored strategies for different populations affected by the COVID-19 pandemic.

The Role of Immunosuppressants, Vaccination, and Monoclonal Antibody Treatment in COVID-19 Outcomes for Liver and Renal Transplant Recipients

Introduction: Post-transplant immunosuppression may leave solid organ transplant (SOT) recipients at an increased risk of SARS-CoV-2 infection and related morbidity. Additionally, the inability to predict any improvement in clinical outcomes offered by a 3-vaccine series suggests the need to consider further therapeutic options such as a fourth mRNA vaccine dose and the use of tixagevimab/cilgavimab for SOT recipients. Demographic Data of LRT Recipients Stratified by Number of Vaccine Doses Before COVID-19 Diagnosis *y: years Variable Response Number of Vaccine Doses Before COVID-19 Diagnosis All 0 1 2 3 (N=255) (N=161) (N=16) (N=56) (N=22) Age Mean (SD), y 57.6 (13.56) 57.1 (13.07) 56.2 (13.37) 57.8 (15.28) 61.5 (12.75) Median, y 59 58 57 61.5 64.5 Gender F, n (%) 108 (42) 66 (41) 4 (25) 27 (48) 11 (50) M, n (%) 147 (58) 95 (59) 12 (75) 29 (52) 11 (50) Race White, n (%) 141 (55) 88 (55) 9 (56) 34 (61) 10 (45) Black, n (%) 104 (41) 65 (40) 7 (44) 22 (39) 10 (45) Hispanic, n (%) 6 (2) 6 (4) 0 (0) 0 (0) 0 (0) Asian, n (%) 4 (2) 2 (1) 0 (0) 0 (0) 2 (9)

Outcomes of COVID-19 in a Large Cohort of Lung Transplant Recipients: A Retrospective Study

Background: Early reports of COVID-19 in lung transplant recipients (LTRs) showed high hospitalization and mortality rates. However, the outcomes of COVID-19 in LTRs since the advent of newer therapies and vaccines have been poorly defined. Methods: We evaluated the risks for SARS-CoV-2-related hospitalization and mortality in a cohort of LTRs at the Henry Ford Lung Transplant Program in Detroit, Michigan during the study period March 2020–March 2022. Univariate logistic regression, followed by multivariable modeling were performed to estimate the odds ratio (OR) with 95% confident intervals (CI). Results: Sixty-four laboratory-confirmed SARS-CoV-2 infections were identified in 59 patients. For the primary analysis of the hospitalization and mortality risks, we included these 59 patients with symptomatic COVID-19. SARS-CoV-2 infections were confirmed with real-time polymerase chain reaction (RT-PCR) from a nasopharynx swab. The mean age (±STD) was 61 (±12), 63% were males, 27% were African Americans, and the time from lung transplant to COVID-19 was 5.5 (±4.8) years. Thirty-four (57.6%) patients were hospitalized, and the inpatient mortality rate was 24% (8/34). A multivariable analysis showed that patients with a higher baseline forced expiratory volume (FEV1) were less likely to be hospitalized (OR = 0.91 and 95% CI 0.87–0.98, p = 0.02). Seventy-five percent (75%;6/8) of patients on invasive mechanical ventilation died, compared with only 8% mortality rate in those without mechanical ventilation (OR = 36.0 and 95% CI 4.2–310.4, p < 0.01). Although a trend toward a higher risk of death was observed in those infected during the Alpha (p = 0.17) and Delta (p = 0.22) waves, no significant risk was detected after adjusting for other covariates. Five LTRs were diagnosed with COVID-19 twice. Thirty of the sixty-four COVID-19 cases (46.8%) occurred in LTRs that had received at least two doses of any of the available mRNA vaccines at a median of 123 days (IQR 98–164 days) after vaccination. Twelve of the thirty (40%) were hospitalized, and four patients (33%) died during their hospitalizations. Conclusions: In our LTR population, the hospitalization and mortality rates associated with COVID-19 were high despite the increased use of new therapies. Vaccine-breakthrough infections were common and were associated with poor outcomes. Studies are needed to determine optimal prevention and therapeutic strategies to improve COVID-19 outcomes in LTRs.

The Prevalence of Post-traumatic Stress Disorder Symptoms, Sleep Problems, and Psychological Distress Among COVID-19 Frontline Healthcare Workers in Taiwan.

The adverse effect of COVID-19 pandemic among individuals has been very disturbing especially among healthcare workers. This study aims to examine the prevalence of post-traumatic stress disorder (PTSD) symptoms, sleep problems, and psychological distress among COVID-19 frontline healthcare workers in Taiwan. Hence, a total of 500 frontline healthcare workers were recruited to participate in this cross-sectional study. They responded to measures on fear of COVID-19, depression, anxiety, stress, insomnia, PTSD, perceived stigma, and self-stigma. The results indicated a prevalence rate of 15.4% for PTSD symptoms, 44.6% for insomnia, 25.6% for depressive symptoms, 30.6% for anxiety symptoms, and 23.4% for stress among the participants. There were significantly positive interrelationships between all these variables. Anxiety symptoms and fear of COVID-19 predicted PTSD whereas symptoms of anxiety, fear of COVID-19, and stress predicted insomnia. The prevalence rates of the psychological problems reveal a worrying view of mental health challenges among Taiwanese frontline healthcare workers. Anxiety symptoms and fear of COVID-19 are the common predictive factors of PTSD and sleep problems suggesting that mental healthcare services for them may help prevent future occurrence of psychological problems by allaying fears of healthcare workers. Therefore, there should be mental healthcare services for healthcare workers during the COVID-19 pandemic.

Application of SARS-CoV-2 antibody sample panel in quality evaluation of test cassettes for colloidal gold lateral flow assay

Objective: To establish a SARS-CoV-2 antibody sample panel and apply to the quality evaluation of test cassettes for colloidal gold lateral flow assay.

Willingness of Taiwan's Healthcare Workers and Outpatients to Vaccinate against COVID-19 during a Period without Community Outbreaks.

To control the spread of the novel coronavirus disease 2019 (COVID-19), COVID-19 vaccination has been quickly developed. However, the COVID-19 pandemic will not be controlled if the COVID-19 vaccination uptake willingness is low. Therefore, the study aim was to explore the COVID-19 vaccination uptake willingness among the outpatient population and healthcare workers in Taiwan during the worldwide pandemic period without community outbreaks. A cross-sectional survey was conducted among healthcare workers (HCWs; n = 500; mean age = 32.96 years) of National Cheng Kung University Hospital (NCKUH) and outpatients (n = 238; mean age = 34.43 years) arriving at NCKUH. We used an online survey conducted between September 24 and 21 November 2020, for healthcare workers, and between 27 October and 31 December 2020, for the outpatient sample. Information regarding willingness to receive vaccination, willingness to rapid test, fear of COVID-19, risk perception, and preventive behaviors was collected in both samples; information regarding willingness to care for patients was collected in healthcare workers. Willingness to receive vaccination was the main variable in the present study; willingness to rapid test, willingness to care for patients, fear of COVID-19, risk perception, and preventive behaviors were the secondary variables in the study. The factors associated with vaccination willingness were identified through logistic regression analysis. The participants' willingness to receive vaccination was low for both healthcare workers (23.4%) and the outpatient sample (30.7%). Similarly, their willingness to take rapid tests was low (23.6% for healthcare workers and 28.6% for outpatient sample). Risk perception (crude odds ratio (COR) = 1.29; 95% confidence interval (CI) = 1.03, 1.63), willingness to take rapid test (COR = 9.24; 95% CI = 5.76, 14.83), and preventive COVID-19 infection behaviors (COR = 2.32; 95% CI = 1.52, 3.56) were significant factors explaining the healthcare workers' willingness to receive vaccination. Willingness to take a rapid test (COR = 8.91; 95% CI = 4.71, 16.87) and preventive COVID-19 infection behaviors (COR = 1.69; 95% CI = 1.09, 2.60) were significant factors explaining the outpatient sample's willingness to receive vaccination. Willingness to vaccinate against COVID-19 among HCWs and outpatients is low due to the relatively safe status of COVID-19 infection in Taiwan. These findings can help policymakers advocate for the effectiveness of and provide transparent information on COVID-19 vaccination uptake in a country/region with a relatively safe COVID-19 outbreak status.

Willingness of Taiwan’s Healthcare Workers and Outpatients to Vaccinate against COVID-19 during a Period without Community Outbreaks

To control the spread of the novel coronavirus disease 2019 (COVID-19), COVID-19 vaccination has been quickly developed. However, the COVID-19 pandemic will not be controlled if the COVID-19 vaccination uptake willingness is low. Therefore, the study aim was to explore the COVID-19 vaccination uptake willingness among the outpatient population and healthcare workers in Taiwan during the worldwide pandemic period without community outbreaks. A cross-sectional survey was conducted among healthcare workers (HCWs;n = 500;mean age = 32.96 years) of National Cheng Kung University Hospital (NCKUH) and outpatients (n = 238;mean age = 34.43 years) arriving at NCKUH. We used an online survey conducted between September 24 and 21 November 2020, for healthcare workers, and between 27 October and 31 December 2020, for the outpatient sample. Information regarding willingness to receive vaccination, willingness to rapid test, fear of COVID-19, risk perception, and preventive behaviors was collected in both samples;information regarding willingness to care for patients was collected in healthcare workers. Willingness to receive vaccination was the main variable in the present study;willingness to rapid test, willingness to care for patients, fear of COVID-19, risk perception, and preventive behaviors were the secondary variables in the study. The factors associated with vaccination willingness were identified through logistic regression analysis. The participants’ willingness to receive vaccination was low for both healthcare workers (23.4%) and the outpatient sample (30.7%). Similarly, their willingness to take rapid tests was low (23.6% for healthcare workers and 28.6% for outpatient sample). Risk perception (crude odds ratio (COR) = 1.29;95% confidence interval (CI) = 1.03, 1.63), willingness to take rapid test (COR = 9.24;95% CI = 5.76, 14.83), and preventive COVID-19 infection behaviors (COR = 2.32;95% CI = 1.52, 3.56) were significant factors explaining the healthcare workers’ willingness to receive vaccination. Willingness to take a rapid test (COR = 8.91;95% CI = 4.71, 16.87) and preventive COVID-19 infection behaviors (COR = 1.69;95% CI = 1.09, 2.60) were significant factors explaining the outpatient sample’s willingness to receive vaccination. Willingness to vaccinate against COVID-19 among HCWs and outpatients is low due to the relatively safe status of COVID-19 infection in Taiwan. These findings can help policymakers advocate for the effectiveness of and provide transparent information on COVID-19 vaccination uptake in a country/region with a relatively safe COVID-19 outbreak status.

Coronavirus pandemic reduced China's CO2 emissions in short-term, while stimulus packages may lead to emissions growth in medium- and long-term.

Coronavirus has confined human activities, which caused significant reductions in coal, oil, and natural gas consumptions in China since January of 2020. We compile industrial, transport, and construction data to estimate the reductions in energy-related CO2 emissions during the first quarter of 2020 in China. Our results show that the fossil fuel related CO2 emissions decreased by 18.7% (182 MtCO2) in the first quarter of 2020 compared with the same period last year, including reductions of 12.2% (92 MtCO2) in industry sectors, 61.9% (62 MtCO2) in transport, and 23.9% (28 MtCO2) in construction. The figure in annual CO2 emission reductions is expected to limit with an estimate of 1.6%. However, to achieve the economic target for the 13th Five-Year-Plan, stimulus packages including investments in "shovel-ready" infrastructure projects issued by China's central and local governments to response the COVID-19 may increase CO2 emissions with a higher speed in the coming years. Thus, sustainable stimulus packages are needed for accelerating China's climate goals.

Analysis of genomic distributions of SARS-CoV-2 reveals a dominant strain type with strong allelic associations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID 19, continues to evolve since its first emergence in December 2019. Using the complete sequences of 1,932 SARS-CoV-2 genomes, various clustering analyses consistently identified six types of the strains. Independent of the dendrogram construction, 13 signature variations in the form of single nucleotide variations (SNVs) in protein coding regions and one SNV in the 5' untranslated region (UTR) were identified and provided a direct interpretation for the six types (types I to VI). The six types of the strains and their underlying signature SNVs were validated in two subsequent analyses of 6,228 and 38,248 SARS-CoV-2 genomes which became available later. To date, type VI, characterized by the four signature SNVs C241T (5'UTR), C3037T (nsp3 F924F), C14408T (nsp12 P4715L), and A23403G (Spike D614G), with strong allelic associations, has become the dominant type. Since C241T is in the 5' UTR with uncertain significance and the characteristics can be captured by the other three strongly associated SNVs, we focus on the other three. The increasing frequency of the type VI haplotype 3037T-14408T-23403G in the majority of the submitted samples in various countries suggests a possible fitness gain conferred by the type VI signature SNVs. The fact that strains missing one or two of these signature SNVs fail to persist implies possible interactions among these SNVs. Later SNVs such as G28881A, G28882A, and G28883C have emerged with strong allelic associations, forming new subtypes. This study suggests that SNVs may become an important consideration in SARS-CoV-2 classification and surveillance.