Discovery and genetic characterization of novel paramyxoviruses from small mammals in Hubei Province, Central China.

Paramyxoviruses are a group of single-stranded, negative-sense RNA viruses, some of which are responsible for acute human disease, including parainfluenza virus, measles virus, Nipah virus and Hendra virus. In recent years, a large number of novel paramyxoviruses, particularly members of the genus Jeilongvirus, have been discovered in wild mammals, suggesting that the diversity of paramyxoviruses may be underestimated. Here we used hemi-nested reverse transcription PCR to obtain 190 paramyxovirus sequences from 969 small mammals in Hubei Province, Central China. These newly identified paramyxoviruses were classified into four clades: genera Jeilongvirus, Morbillivirus, Henipavirus and Narmovirus, with most of them belonging to the genus Jeilongvirus. Using Illumina sequencing and Sanger sequencing, we successfully recovered six near-full-length genomes with different genomic organizations, revealing the more complex genome content of paramyxoviruses. Co-divergence analysis of jeilongviruses and their known hosts indicates that host-switching occurred more frequently in the evolutionary histories of the genus Jeilongvirus. Together, our findings demonstrate the high prevalence of paramyxoviruses in small mammals, especially jeilongviruses, and highlight the diversity of paramyxoviruses and their genome content, as well as the evolution of jeilongviruses.

Diversity and genetic characterization of orthohantavirus from small mammals and humans during 2012-2022 in Hubei Province, Central China.

Hemorrhagic fever with renal syndrome (HFRS) is a significant public health problem in Hubei Province, China, where a novel strain of orthohantavirus, HV004, was reported in 2012. However, no systematic study has investigated the prevalence and variation of orthohantavirus in rodents and humans. Herein, 2137 small mammals were collected from ten HFRS epidemic areas in Hubei Province from 2012 to 2022, and 143 serum samples from patients with suspected hemorrhagic fever were collected from two hospitals from 2017 to 2021. Orthohantavirus RNA was recovered from 134 lung tissue samples from five rodent species, with a 6.27 % prevalence, and orthohantavirus was detected in serum samples from 25 patients. Genetic analyses revealed that orthohantavirus hantanense (HTNV), orthohantavirus seoulense (SEOV), and orthohantavirus dabieshanense (DBSV) are co-circulating in rodents in Hubei, and HTNV and SEOV were identified in patient serum. Phylogenetic analysis showed that most of the HTNV sequences were clustered with HV004, indicating that HV004-like orthohantavirus was the main HNTV subtype in rodents. Two genetic reassortments and six recombination events were observed in Hubei orthohantaviruses. In summary, this study identified the diversity of orthohantaviruses circulating in Hubei over the past decade, with the HV004-like subtype being the main genotype in rodents and patients. These findings highlight the need for continued attention and focus on orthohantaviruses, especially concerning newly identified strains.

Enhanced external counter pulsation therapy in patients with symptomatic and severe intracranial steno-occlusive disease: a randomized clinical trial protocol.

Intracranial stenosis is prevalent among Asians and constitutes a common cause of cerebral ischemia. While the best medical therapy carries stroke recurrence rates in excess of 10% per year, trials with intracranial stenting have been associated with unacceptable peri-procedural ischemic events. Cerebral ischemic events are strongly related to the severity of intracranial stenosis, which is high in patients with severe intracranial stenosis with poor vasodilatory reserve. Enhanced External Counter Pulsation (EECP) therapy is known to improve myocardial perfusion by facilitating the development of collateral blood vessels in the heart. In this randomized clinical trial, we evaluate whether EECP therapy may be useful in patients with severe stenosis of intracranial internal carotid (ICA) or middle cerebral artery (MCA). The review of literature, methods of evaluation, status of currently used therapeutic approaches, and trial protocol have been presented. Clinical trial registration: ClinicalTrials.gov, Identifier: NCT03921827.

A sublethal dose of neonicotinoid imidacloprid precisely sensed and detoxified by a C-minus odorant-binding protein 17 highly expressed in the legs of Apis cerana.

As a native honeybee species in East Asia, Apis cerana is essential for the stability of local agricultural and plant ecosystems by its' olfactory system for searching nectar and pollen sources. Odorant-binding proteins (OBPs) existing in the insect's olfactory system can recognize environmental semiochemicals. It was known that sublethal doses of neonicotinoid insecticides could still cause a variety of physiological and behavioral abnormalities in bees. However, the molecular mechanism of A. cerana sensing and response for insecticide has not been further investigated. In this study, we found an A. cerana OBP17 gene significantly up-regulated expressed after exposure to sublethal doses of imidacloprid based on the transcriptomics results. The spatiotemporal expression profiles showed that OBP17 was highly expressed in the legs. Competitive fluorescence binding assays showed that OBP17 had the special and high binding affinity to imidacloprid among the 24 candidate semiochemicals, and the KA value of OBP17 binding with imidacloprid reached the maximum (6.94 × 104 L/mol) at low-temperature. Thermodynamic analysis showed that the quenching mechanism changed from dynamic to static binding interaction with the increasing temperature. Meanwhile, the force changed from hydrogen bond and van der Waals force to hydrophobic interaction and electrostatic force, indicating the interaction exhibits variability and flexibility. Molecular docking showed that Phe107 contributed the most energy. RNA interference (RNAi) results showed that OBP17 knockdown significantly enhanced the electrophysiological response of the bees' forelegs to imidacloprid. Our study indicated that OBP17 could precisely touch and sense sublethal doses of neonicotinoid imidacloprid in the natural environment through its high expression in legs, and the upregulation expression of OBP17 exposure to imidacloprid probably implied that it participate in the detoxification processes of A. cerana. Also, our research enriches the theoretical knowledge of the sensing and detoxifying activities of non-target insects' olfactory sensory system to environmental sublethal doses of systemic insecticides.

A rare case of bladder cancer that metastasized to brain, heart, and lung lymph nodes benefited from immunotherapy.

Bladder cancer is a common malignant tumor of the genitourinary system, with the primary cause of death being metastasis. The most common metastatic sites are the lymph nodes, liver, lung, bone, peritoneum, pleura, kidney, adrenal gland, and the intestine. Brain and heart metastases are rare. In this report, we describe a patient who had pulmonary lymph node metastases more than a year after being diagnosed with bladder cancer, followed by brain and cardiac metastases more than two years later. Following the failure of standard first-line chemotherapy, the patient accepted 6 cycles of tislelizumab immunotherapy. The re-examination revealed that the bilateral frontal brain metastases had vanished, the right temporal lobe metastases had been greatly decreased, the neurological symptoms had been alleviated, and the cardiac metastases had disappeared. This is a rare clinical case with encouraging effects of tislelizumab and can serve as a model for the treatment of similar patients.

Oxidative functionalization of alkylidenecyclopropanes and alkylidenecyclobutanes: a versatile platform to access nitrated cyclopropanes and cyclobutanes.

A divergent radical nitration of alkylidenecyclopropanes (ACPs) and alkylidenecyclobutanes (ACBs) with Fe(NO3)3·9H2O or AgNO2 has been achieved, affording three categories of products including ß-nitro alcohol, α-nitro ketone and nitro nitratosation products with yields up to 90%. Particularly, the cyclopropyl and cyclobutyl rings were conserved in the products. The applicability of this method was demonstrated by the scale-up experiment and reduction of the nitro into an amino group. Preliminary mechanistic studies suggested that the nitro radical was involved in the reaction process.

Nestin+/CD31+ cells in the hypoxic perivascular niche regulate glioblastoma chemoresistance by upregulating JAG1 and DLL4.

BACKGROUND: Failure of glioblastoma (GBM) therapy is often ascribed to different types of glioblastoma stem-like cell (GSLC) niche; in particular, a hypoxic perivascular niche (HPVN) is involved in GBM progression. However, the cells responsible for HPVNs remain unclear. METHODS: Immunostaining was performed to determine the cells involved in HPVNs. A hypoxic chamber and 3-dimensional (3D) microfluidic chips were designed to simulate a HPVN based on the pathological features of GBM. The phenotype of GSLCs was evaluated by fluorescence scanning in real time and proliferation and apoptotic assays. The expression of JAG1, DLL4, and Hes1 was determined by immunostaining, ELISA, Western blotting, and quantitative PCR. Their clinical prognostic significance in GBM HPVNs and total tumor tissues were verified by clinical data and The Cancer Genome Atlas databases. RESULTS: Nestin+/CD31+ cells and pericytes constitute the major part of microvessels in the HPVN, and the high ratio of nestin+/CD31+ cells rather than pericytes are responsible for the poor prognosis of GBM. A more real HPVN was simulated by a hypoxic coculture system in vitro, which consisted of 3D microfluidic chips and a hypoxic chamber. Nestin+/CD31+ cells in the HPVN were derived from GSLC transdifferentiation and promoted GSLC chemoresistance by providing more JAG1 and DLL4 to induce downstream Hes1 overexpression. Poor GBM prognosis correlated with Hes1 expression of tumor cells in the GBM HPVN, and not with total Hes1 expression in GBM tissues. CONCLUSIONS: These results highlight the critical role of nestin+/CD31+ cells in HPVNs that acts in GBM chemoresistance and reveal the distinctive prognostic value of these molecular markers in HPVNs.

Asian-Pacific perspective on the psychological well-being of healthcare workers during the evolution of the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to significant strain on front-line healthcare workers. AIMS: In this multicentre study, we compared the psychological outcomes during the COVID-19 pandemic in various countries in the Asia-Pacific region and identified factors associated with adverse psychological outcomes. METHOD: From 29 April to 4 June 2020, the study recruited healthcare workers from major healthcare institutions in five countries in the Asia-Pacific region. A self-administrated survey that collected information on prior medical conditions, presence of symptoms, and scores on the Depression Anxiety Stress Scales and the Impact of Events Scale-Revised were used. The prevalence of depression, anxiety, stress and post-traumatic stress disorder (PTSD) relating to COVID-19 was compared, and multivariable logistic regression identified independent factors associated with adverse psychological outcomes within each country. RESULTS: A total of 1146 participants from India, Indonesia, Singapore, Malaysia and Vietnam were studied. Despite having the lowest volume of cases, Vietnam displayed the highest prevalence of PTSD. In contrast, Singapore reported the highest case volume, but had a lower prevalence of depression and anxiety. In the multivariable analysis, we found that non-medically trained personnel, the presence of physical symptoms and presence of prior medical conditions were independent predictors across the participating countries. CONCLUSIONS: This study highlights that the varied prevalence of psychological adversity among healthcare workers is independent of the burden of COVID-19 cases within each country. Early psychological interventions may be beneficial for the vulnerable groups of healthcare workers with presence of physical symptoms, prior medical conditions and those who are not medically trained.

Identification and characterization of Jingmen tick virus in rodents from Xinjiang, China.

Jingmen tick virus (JMTV) is a recently identified virus which provides an unexpected connection between segmented and unsegmented RNA viruses. Recent investigations reveal that JMTV including JMTV-like virus (Alongshan virus) could be associated with human disease, suggesting the significance of JMTV in public health. To better understand the genetic diversity and host range of JMTV, a total of 164 rodents representing 8 species were collected in Qapqal Xibe county of Xinjiang Uygur Autonomous Region, China, and were screened for JMTVs using RT- PCR. Consequently, JMTV was identified in 42 rodents including 23 Microtus arvalis voles (24.5%), 9 Apodemus uralensis mice (29.0%), 5 Mus musculus mice, 1 Rhombomys opimus gerbil, 1 Meriones tamariscinus gerbil, 1 Meriones libycus gerbil, 1 Cricetulus migratorius hamster and 1 Microtus gregalis vole. Interestingly, nearly complete genome sequences were successfully recovered from 7 JMTV positive samples. Although the newly identified rodent JMTVs were closely related to those previously identified in ticks from China, based on the phylogenetic analysis of the S1, S2 and S3 segments, the newly identified rodent viruses clustered into two genetic groups. One group comprised of viruses only found in M. arvalis, while another group included viruses from A. uralensis, C. migratorius and M. gregalis. However, all rodent viruses clustered together in the S4 tree. Considering rodents live in close proximity to humans, more efforts are needed to investigate the role of rodents in the evolution and transmission of JMTV in nature.

A multinational, multicentre study on the psychological outcomes and associated physical symptoms amongst healthcare workers during COVID-19 outbreak.

OBJECTIVE: Since the declaration of the coronavirus 2019 (COVID-19) outbreak as pandemic, there are reports on the increased prevalence of physical symptoms observed in the general population. We investigated the association between psychological outcomes and physical symptoms among healthcare workers. METHODS: Healthcare workers from 5 major hospitals, involved in the care for COVID-19 patients, in Singapore and India were invited to participate in a study by performing a self-administered questionnaire within the period of February 19 to April 17, 2020. Healthcare workers included doctors, nurses, allied healthcare workers, administrators, clerical staff and maintenance workers. This questionnaire collected information on demographics, medical history, symptom prevalence in the past month, Depression Anxiety Stress Scales (DASS-21) and the Impact of Events Scale-Revised (IES-R) instrument. The prevalence of physical symptoms displayed by healthcare workers and the associations between physical symptoms and psychological outcomes of depression, anxiety, stress, and post-traumatic stress disorder (PTSD) were evaluated. RESULTS: Out of the 906 healthcare workers who participated in the survey, 48 (5.3%) screened positive for moderate to very-severe depression, 79 (8.7%) for moderate to extremely-severe anxiety, 20 (2.2%) for moderate to extremely-severe stress, and 34 (3.8%) for moderate to severe levels of psychological distress. The commonest reported symptom was headache (32.3%), with a large number of participants (33.4%) reporting more than four symptoms. Participants who had experienced symptoms in the preceding month were more likely to be older, have pre-existing comorbidities and a positive screen for depression, anxiety, stress, and PTSD. After adjusting for age, gender and comorbidities, it was found that depression (OR 2.79, 95% CI 1.54-5.07, p = 0.001), anxiety (OR 2.18, 95% CI 1.36-3.48, p = 0.001), stress (OR 3.06, 95% CI 1.27-7.41, p = 0.13), and PTSD (OR 2.20, 95% CI 1.12-4.35, p = 0.023) remained significantly associated with the presence of physical symptoms experienced in the preceding month. Linear regression revealed that the presence of physical symptoms was associated with higher mean scores in the IES-R, DASS Anxiety, Stress and Depression subscales. CONCLUSIONS: Our study demonstrates a significant association between the prevalence of physical symptoms and psychological outcomes among healthcare workers during the COVID-19 outbreak. We postulate that this association may be bi-directional, and that timely psychological interventions for healthcare workers with physical symptoms should be considered once an infection has been excluded.

Blue light fromelectronic devicesmay bean important factorforvitreousfloaters.

At present, researchers are still debating the effect of blue light on the eyes.Studies have shown thatwhile blue lighthelpsto maintain normal biological rhythms,excessive blue light radiation mayinduce fundus lesions. The preliminary survey shows that the incidence of vitreous floaters is high among digital device users, electronic screens such as smart phones, iPad, and liquidcrystal displays (LCDs) emit blue light that may accelerates vitreous degeneration, resulting in vitreous opacity and increased floaters. Further research is needed to clarify the effects of blue light on the vitreous.

Accuracy of matrix-assisted LASER desorption ionization-time of flight mass spectrometry for identification of Candida.

BACKGROUND: Candida is a fungus that causes various types of candidemia, which is the fourth major infectious disease of the blood system. MALDI-TOF-MS is a simple and rapid detection instrument. The aim of the present study was to verify the accuracy of MALDI-TOF-MS in detecting Candida. METHOD: A pooled analysis of articles on MALDI-TOF-MS for diagnosis of candidemia was performed. The quality of original research was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines. Stata 12.0 software was used to merge the correct identification rates of Candida and Candida subspecies and obtain pooled sensitivity and specificity of the diagnostic methods. Heterogeneity was found in the subgroup analysis of the included articles. Hence, we explored the factors causing the heterogeneity and its impact on the overall situation. Sensitivity analysis was used to examine the effect of Candida level on total response. Egger's test was used to evaluate the publication bias of the included articles. RESULTS: A total of 16 articles in Pubmed, 79 articles in Embase, 1 article in Cochrane Library, 30 articles in Web of Science and 3 from other sources were identified, of which 10 articles were included based on the inclusion and exclusion criteria. The overall identification accuracy was 100%. CONCLUSION: The accuracy of MALDI-TOF-MS for the identification of Candida was 100%. Further research is necessary to determine whether MALDI-TOF-MS can be used as a clinical diagnostic standard for the identification of Candida.

Identification and characterization of a novel subtype of Tula virus in Microtus arvalis obscurus voles sampled from Xinjiang, China.

Although most of Arvicolinae associated hantaviruses can not cause disease in humans, hemorrhagic fever with renal syndrome (HFRS) cases caused by Tula virus (TULV) have been described in Europe since 2002. In addition to Europe, TULV was also identified in the Microtus arvalis obscurus voles sampled from Kazakhstan, which shares borders with China. To gain more insight into the molecular epidemiology of TULV, a total of 365 rodents representing 7 species of 4 subfamily (Arvicolinae, Murinae, Gerbillinae, and Cricetinae) were captured in Qapqal county, Xinjiang, northwest China. Hantavirus RNA was recovered from 40 lung tissue samples of M. arvalis obscurus, with the prevalence of 10.96%. Genetic analysis revealed that all recovered viral sequences were most closely related to those of TULV, but exhibited >11% nucleotide differences from all currently known TULV, suggesting that they may represent a new subtype of TULV. In the S tree, the newly identified viruses formed a distinct lineage and showed a close evolutionary relationship with those sampled from Southwestern Siberia and Kazakhstan. However, they exhibited a different clustering pattern in both the M and the L trees, suggesting the possibility of genetic reassortment. Finally, the recombination event was also observed in Xinjiang TULV viruses. In sum, all these data reveal a complex evolutionary history of TULV in Central Asia.

[Effects of protein kinase C activity on CD44 expression and subcellular distribution in human erythrocytes].

The study was aimed to investigate the effects of protein kinase C (PKC) on standard type CD44 expression and subcellular distribution in human erythrocytes. PKC activity was detected by the incorporation of [gamma-(32)P]-ATP into exogenous substrate, phosphorylation of CD44 was determined by autoradiograph, distribution of CD44 was observed by indirect immunofluorescence, and expression of CD44 was analyzed by flow cytometry. The results showed that PKC activity reached the maximal level at 30 minutes after treatment with phorbol-myristate-acetate (PMA), and the peak of CD44 phosphorylation and CD44 expression appeared at the same time, which all increased significantly as compared with control group (p < 0.001). PKC activation resulted in CD44 aggregation on membrane and colocalization of PKC and CD44. Calphostin C could inhibit the above reaction resulted from PKC activation. It is concluded that PKC activation can up-regulate CD44 expression by phosphorylation, and result in the coherent migration and colocalization of CD44 and PKC in human erythrocytes.