Potential COVID-19 remedies from repurposed drugs and herbal small RNAs.

To date, SARS-CoV-2 has caused millions of deaths, but the choice of treatment is limited. We previously established a platform for identifying Food and Drug Administration (FDA)-approved repurposed drugs for avian influenza A virus infections that could be used for coronavirus disease 2019 (COVID-19) treatment. In this study, we analyzed blood samples from two cohorts of 63 COVID-19 patients, including 19 patients with severe disease. Among the 39 FDA-approved drugs we identified for COVID-19 therapy in both cohorts, 23 drugs were confirmed by literature mining data, including 14 drugs already under COVID-19 clinical trials and 9 drugs reported for COVID-19 treatments, suggesting the remaining 16 FDA-approved drugs may be candidates for COVID-19 therapy. Additionally, we previously reported that herbal small RNAs (sRNAs) could be effective components in traditional Chinese medicine (TCM) for treating COVID-19. Based on the abundance of sRNAs, we screened the 245 TCMs in the Bencao (herbal) sRNA Atlas that we had previously established, and we found that the top 12 TCMs for COVID-19 treatment was consistent across both cohorts. We validated the efficiency of the top 30 sRNAs from each of the top 3 TCMs for COVID-19 treatment in poly(I:C)-stimulated human non-small cell lung cancer cells (A549 cells). In conclusion, our study recommends potential COVID-19 remedies using FDA-approved repurposed drugs and herbal sRNAs from TCMs.

Using social media data to assess the impact of COVID-19 on mental health in China.

BACKGROUND: The outbreak and rapid spread of coronavirus disease 2019 (COVID-19) not only caused an adverse impact on physical health, but also brought about mental health problems among the public. METHODS: To assess the causal impact of COVID-19 on psychological changes in China, we constructed a city-level panel data set based on the expressed sentiment in the contents of 13 million geotagged tweets on Sina Weibo, the Chinese largest microblog platform. RESULTS: Applying a difference-in-differences approach, we found a significant deterioration in mental health status after the occurrence of COVID-19. We also observed that this psychological effect faded out over time during our study period and was more pronounced among women, teenagers and older adults. The mental health impact was more likely to be observed in cities with low levels of initial mental health status, economic development, medical resources and social security. CONCLUSIONS: Our findings may assist in the understanding of mental health impact of COVID-19 and yield useful insights into how to make effective psychological interventions in this kind of sudden public health event.

Identification of amitriptyline HCl, flavin adenine dinucleotide, azacitidine and calcitriol as repurposing drugs for influenza A H5N1 virus-induced lung injury.

Infection with avian influenza A H5N1 virus results in acute lung injury (ALI) and has a high mortality rate (52.79%) because there are limited therapies available for treatment. Drug repositioning is an economical approach to drug discovery. We developed a method for drug repositioning based on high-throughput RNA sequencing and identified several drugs as potential treatments for avian influenza A H5N1 virus. Using high-throughput RNA sequencing, we identified a total of 1,233 genes differentially expressed in A549 cells upon H5N1 virus infection. Among these candidate genes, 79 drug targets (corresponding to 59 approved drugs) overlapped with the DrugBank target database. Twenty-two of the 41 commercially available small-molecule drugs reduced H5N1-mediated cell death in cultured A549 cells, and fifteen drugs that protected A549 cells when administered both pre- and post-infection were tested in an H5N1-infection mouse model. The results showed significant alleviation of acute lung injury by amitriptyline HCl (an antidepressant drug), flavin adenine dinucleotide (FAD; an ophthalmic agent for vitamin B2 deficiency), azacitidine (an anti-neoplastic drug) and calcitriol (an active form of vitamin D). All four agents significantly reduced the infiltrating cell count and decreased the lung injury score in H5N1 virus-infected mice based on lung histopathology, significantly improved mouse lung edema by reducing the wet-to-dry weight ratio of lung tissue and significantly improved the survival of H5N1 virus-infected mice. This study not only identifies novel potential therapies for influenza H5N1 virus-induced lung injury but also provides a highly effective and economical screening method for repurposing drugs that may be generalizable for the prevention and therapy of other diseases.

Ringing-free fast Fourier single-pixel imaging.

Fourier single-pixel imaging (FSI) allows an image to be reconstructed by acquiring the Fourier spectrum of the image using a single-pixel detector. Fast FSI is typically achieved by acquiring a truncated Fourier spectrum, that is, only low-frequency Fourier coefficients are acquired, with the high-frequency coefficients discarded. However, the truncation of the Fourier spectrum leads to undesirable ringing artifacts in the resulting image. Ringing artifacts produce false edges in the image and reduce the image contrast, resulting in image quality degeneration. The artifact is particularly severe in dynamic FSI, where the sampling ratio is generally ultra-low. We propose an effective and fast deringing algorithm to achieve ringing-free fast FSI. The algorithm eliminates ringing artifacts through 2D sub-pixel shifting and preserves image details through image fusion. Both static and dynamic imaging results demonstrate that the proposed method can reconstruct ringing-free images from under-sampled data in FSI. The deringing algorithm not only provides FSI with the capability of fast high-quality single-pixel imaging but also might prove its applicability in other areas, such as Fourier-based data compression algorithms.

The association between blood albumin level and cardiovascular complications and mortality risk in ICU patients with CKD.

BACKGROUND: Studies involving the association of blood albumin with prognosis in patients with chronic kidney disease (CKD) during intensive care unit (ICU) were scarce. AIM: We investigated whether reduced blood albumin level independently associated with an increased risk of cardiovascular (CV) complications and 1-year mortality risk in ICU patients with CKD. METHODS: The Medical Information Mart for Intensive Care III (MIMIC-III) database was used. Disease diagnosis and death information among a number of 925 ICU patients with CKD, who have been measured for blood biochemistry, were recorded. Here, multivariable logistic regression Models were structured to evaluate the associations between blood albumin levels (first value on admission, maximum and minimum value during ICU) and risks for CV complications and 1-year mortality among these CKD patients. RESULTS: In 925 CKD patients, the number of CV complication with heart failure (HF), myocardial infarction (MI) or stroke was 470 (50.8%). 406 (43.9%) patients were dead during the follow-up of 1 year after patients were discharged. Our smooth curve results suggested a curvilinear relation on association between blood albumin level and risk of CV complications. The "inflection point" of blood albumin level that patients were at highest risk of CV complications was 3.4 g/dL. The almost linear relationship with a downward trend was observed on the association between blood albumin level and 1-year mortality risk. We found that reduced blood albumin level contributed to lower risk for CV complications and higher risk for 1-year mortality respectively when blood albumin levels in CKD patients were below 3.4 g/dL. Additionally, albumin therapy had an obvious modifying effect on the independent association, suggesting a possible improved effect of albumin therapy on risk of CV complications and 1-year mortality risk in these CKD patients. CONCLUSIONS: Our study reported that reduced blood albumin levels in CKD patients during ICU were related to lower risk for CV complications and increased risk of 1-year mortality.

The mediating effect of air quality on the association between human mobility and COVID-19 infection in China.

BACKGROUND: Previous studies have found that human mobility restrictions could not only prevent the spread of COVID-19, but also improve the air quality because of the reduction of industrial production, transportation and traffic. It is noteworthy that air quality is also closely related to the risk of COVID-19 infection. Therefore, we aimed to assess the mediating role of air quality on the association between human mobility and the infection caused by this novel coronavirus. METHODS: We collected daily confirmed cases, human mobility data, air quality data and meteorological variables in 120 cities from China between January 23, 2020 and February 29, 2020. We applied the generalized additive model to examine the association of human mobility index with COVID-19 confirmed cases, and to assess the mediating effects of air quality index and each pollutant. RESULTS: We observed a significant positive relationship between human mobility index and the daily counts of COVID-19 confirmed cases. A unit increase in human mobility index (lag0-14) was associated with a 6.45% increase in daily COVID-19 confirmed cases, and air quality index significantly mediated 19.47% of this association. We also observed a positive relationship between human mobility index and air quality index. In the pollutant level analyses, we found significant mediating effects of PM2.5, PM10, and NO2. CONCLUSIONS: Our study suggests that limiting human movements could reduce COVID-19 cases by improving air quality besides decreasing social contact.

[Risk factors for early castration-resistant prostate cancer after androgen deprivation therapy for bone-metastatic prostate cancer].

OBJECTIVE: To investigate the risk factors for early castration-resistant prostate cancer (CRPC) after androgen deprivation therapy (ADT) in patients primarily diagnosed with bone-metastatic prostate cancer (BMPC). METHODS: We retrospectively analyzed the clinical data on 97 cases of primarily diagnosed BMPC treated in our hospital between January 2010 and May 2016. We included the patients without CRPC in group A and those with CRPC found within 12 months after ADT in group B. We obtained clinical data from the two groups of patients, including preoperative levels of hemoglobin, C-reactive protein and serum prostate-specific antigen (PSA), prostate volume, incidence rates of hypertension and diabetes mellitus, long-term use of aspirin or metformin, methods of biopsy and castration, Gleason scores, anti-androgen drugs, and radiotherapy with 89SrCl2, which were subjected to uni- or multivariate logistic regression analysis. RESULTS: CRPC developed in 48 (49.48%) of the 97 patients within 12 months after ADT. Univariate analysis showed the preoperative hemoglobin level, Gleason scores and biopsy by transurethral plasmakinetic resection of the prostate (TUPKRP) to be the risk factors for early CRPC, and multivariate logistic regression analysis identified two independent risk factors for it, which were the Gleason score (P = 0.010) and TUPKRP (P = 0.002). CONCLUSIONS: The incidence rate of early CRPC is high in BMPC patients within 12 months after ADT, for which the independent risk factors include biopsy by TUPKRP and Gleason scores.

Neuraminidase of Influenza A Virus Binds Lysosome-Associated Membrane Proteins Directly and Induces Lysosome Rupture.

UNLABELLED: As a recycling center, lysosomes are filled with numerous acid hydrolase enzymes that break down waste materials and invading pathogens. Recently, lysosomal cell death has been defined as "lysosomal membrane permeabilization and the consequent leakage of lysosome contents into cytosol." Here, we show that the neuraminidase (NA) of H5N1 influenza A virus markedly deglycosylates and degrades lysosome-associated membrane proteins (LAMPs; the most abundant membrane proteins of lysosome), which induces lysosomal rupture, and finally leads to cell death of alveolar epithelial carcinoma A549 cells and human tracheal epithelial cells. The NA inhibitors peramivir and zanamivir could effectively block the deglycosylation of LAMPs, inhibit the virus cell entry, and prevent cell death induced by the H5N1 influenza virus. The NA of seasonal H1N1 virus, however, does not share these characteristics. Our findings not only reveal a novel role of NA in the early stage of the H5N1 influenza virus life cycle but also elucidate the molecular mechanism of lysosomal rupture crucial for influenza virus induced cell death. IMPORTANCE: The integrity of lysosomes is vital for maintaining cell homeostasis, cellular defense and clearance of invading pathogens. This study shows that the H5N1 influenza virus could induce lysosomal rupture through deglycosylating lysosome-associated membrane proteins (LAMPs) mediated by the neuraminidase activity of NA protein. NA inhibitors such as peramivir and zanamivir could inhibit the deglycosylation of LAMPs and protect lysosomes, which also further interferes with the H5N1 influenza virus infection at early stage of life cycle. This work is significant because it presents new concepts for NA's function, as well as for influenza inhibitors' mechanism of action, and could partially explain the high mortality and high viral load after H5N1 virus infection in human beings and why NA inhibitors have more potent therapeutic effects for lethal avian influenza virus infections at early stage.

Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis.

Adrenocorticotrophin (ACTH)-secreting pituitary adenoma, also known as Cushing disease (CD), is rare and causes metabolic syndrome, cardiovascular disease and osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD is still unclear because of a lack of human cell lines and animal models. Here, we study 106 clinical characteristics and gene expression changes from 118 patients, the largest cohort of CD in a single-center. RNA deep sequencing is used to examine genotypic changes in nine paired female ACTH-secreting pituitary adenomas and adjacent nontumorous pituitary tissues (ANPT). We develop a novel analysis linking disease clinical characteristics and whole transcriptomic changes, using Pearson Correlation Coefficient to discover a molecular network mechanism. We report that osteoporosis is distinguished from the phenotype and genotype analysis. A cluster of genes involved in osteoporosis is identified using Pearson correlation coefficient analysis. Most of the genes are reported in the bone related literature, confirming the feasibility of phenotype-genotype association analysis, which could be used in the analysis of almost all diseases. Secreted phosphoprotein 1 (SPP1), collagen type I α 1 chain (COL1A1), 5'-nucleotidase ecto (NT5E), HtrA serine peptidase 1 (HTRA1) and angiopoietin 1 (ANGPT1) and their signalling pathways are shown to be involved in osteoporosis in CD patients. Our discoveries provide a molecular link for osteoporosis in CD patients, and may open new potential avenues for osteoporosis intervention and treatment.

Downregulation of Insulin-like growth factor binding protein 6 is associated with ACTH-secreting pituitary adenoma growth.

BACKGROUND: Adrenocorticotrophic hormone (ACTH)-dependent Cushing's syndrome, called Cushing disease, is caused by a corticotroph tumor of the pituitary gland. Insulin-like growth factor binding protein 6 (IGFBP6), which regulates insulin-like growth factor (IGF) activity and inhibits several IGF2-dependent cancer growths, plays a pivotal role in the tumorigenesis of malignancy, but its roles in ACTH-secreting pituitary adenomas remain unclear. OBJECTIVE: To investigate IGFBP6 expression in ACTH-secreting pituitary adenomas, and its involvement in tumor growth. METHODS: Sporadic ACTH-secreting pituitary adenomas specimens (n = 41) and adjacent non-tumorous pituitary tissues (n = 9) were collected by transphenoidal surgery. IGFBP6 expression was assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and validated by Western blotting. Associations of IGFBP6 expression with maximum tumor diameter or Ki-67 labeling index were evaluated in ACTH-secreting pituitary adenomas. RESULTS: IGFBP6 mRNA and protein expression were both decreased in ACTH-secreting pituitary adenomas, compared to adjacent non-tumorous pituitary tissues (P < 0.01). IGFBP6 expression was correlated inversely with maximum tumor diameter (Rho = -0.53, P < 0.0001) and Ki-67 levels (Rho = -0.52, P < 0.05). Moreover, IGFBP6 downregulation activated PI3 K-AKT-mTOR pathway in ACTH-secreting pituitary adenomas. CONCLUSIONS: IGFBP6 attenuation in ACTH-secreting pituitary adenomas is associated with tumor growth, through activation of PI3K-AKT-mTOR pathway. The finding underlies IGFBP6 roles in Cushing disease and would potentially provide a novel target of medical therapies.

Herbal small RNAs in patients with COVID-19 linked to reduced DEG expression.

In China, more than 80% of patients with coronavirus disease 2019 (COVID-19) received traditional Chinese medicine (TCM) as a treatment and their clinical efficacy have been reported. However, the underlying molecular mechanism remains unclear. Previous studies have identified herbal small RNAs (sRNAs) as novel functional components. In this study, a cohort of 22 patients with COVID-19 treated with Toujie Quwen (TQ) granules was analyzed. We observed thousands of herbal small RNAs that entered the blood cells of patients after the consumption of TQ granules. In response to this treatment, the reduced differentially expressed genes (DEGs) were highly correlated with the predicted target genes of the most prevalent herbal sRNAs detected in the blood. Moreover, the predicted target genes of the top 30 sRNAs from each of the 245 TCMs in the Bencao sRNA Atlas overlapped with 337 upregulated DEGs in patients with mild COVID-19, and 33 TCMs, with more than 50% overlapping genes were identified as effective TCMs. These predicted target genes of top 30 sRNAs from Juhong, Gualoupi and Foshou were confirmed experimentally. Our results not only elucidated a novel molecular mechanism of TCM potential clinical efficacy for COVID-19 patients, but also provided 33 effective COVID-19 TCMs for prescription optimization.

Levistilide A ameliorates neuroinflammation via inhibiting JAK2/STAT3 signaling for neuroprotection and cognitive improvement in scopolamine-induced Alzheimer's disease mouse model.

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with cognitive impairment and dementia, which has become a major public health problem. There are no effective therapeutic agents used to treat AD in clinic for the extremely complex pathogenesis. Here we identify Levistilide A (LA), one of the major active natural terpene lactone constituents from Chinese herbal medicine Angelicae sinensis and Chuanxiong Rhizoma, as a potent neuroinflammation inhibitor for neuroprotection and cognitive improvement of AD. We show that LA suppresses neuronal apoptosis, restores cholinergic system function, and lowers neuroinflammation in vivo to improve scopolamine (SCOP)-induced learning and memory deficits. In addition, LA inhibits the release of IL-1ß, IL-6 and TNF-α, while increasing the production of IL-4 and IL-10 for anti-inflammatory effects in LPS or Aß-induced BV2 and HMC3 cells. Furthermore, the conditioned medium (CM) from LA-treated BV2 or HMC3 cells enhances the viability of SH-SY5Y and HT-22 cells, and LA reverses M1 to M2 phenotype transformation of BV2 and HMC3 cells accompanied by the inhibited Iba-1 expression and mRNA level of IL-1ß, IL-6, TNF-α and NOS2, and the increased expression of ARG1, CD206 and CD163. Mechanistically, we analyze JAK2/STAT3 signaling as possible targets of LA using network pharmacology approaches, and further experimentally validate that LA inhibits the phosphorylation of JAK2 and STAT3, and STAT3 expression within nucleus both in vitro and in vivo. Collectively, we identify LA as a potential neuroinflammation inhibitor for neuroprotection and cognitive improvement, which is expected to be a candidate for AD therapy.

Orally administered BZL-sRNA-20 oligonucleotide targeting TLR4 effectively ameliorates acute lung injury in mice.

The global COVID-19 pandemic emerged at the end of December 2019. Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are common lethal outcomes of bacterial lipopolysaccharide (LPS), avian influenza virus, and SARS-CoV-2. Toll-like receptor 4 (TLR4) is a key target in the pathological pathway of ARDS and ALI. Previous studies have reported that herbal small RNAs (sRNAs) are a functional medical component. BZL-sRNA-20 (Accession number: B59471456; Family ID: F2201.Q001979.B11) is a potent inhibitor of Toll-like receptor 4 (TLR4) and pro-inflammatory cytokines. Furthermore, BZL-sRNA-20 reduces intracellular levels of cytokines induced by lipoteichoic acid (LTA) and polyinosinic-polycytidylic acid (poly (I:C)). We found that BZL-sRNA-20 rescued the viability of cells infected with avian influenza H5N1, SARS-CoV-2, and several of its variants of concern (VOCs). Acute lung injury induced by LPS and SARS-CoV-2 in mice was significantly ameliorated by the oral medical decoctosome mimic (bencaosome; sphinganine (d22:0)+BZL-sRNA-20). Our findings suggest that BZL-sRNA-20 could be a pan-anti-ARDS ALI drug.

A comprehensive analysis of the Bencao (herbal) small RNA Atlas reveals novel RNA therapeutics for treating human diseases.

Cross-kingdom herbal miRNA was first reported in 2012. Using a modified herbal extraction protocol, we obtained 73,677,287 sequences by RNA-seq from 245 traditional Chinese Medicine (TCM), of which 20,758,257 were unique sequences. We constructed a Bencao (herbal) small RNA (sRNA) Atlas ( http://bencao.bmicc.cn ), annotated the sequences by sequence-based clustering, and created a nomenclature system for Bencao sRNAs. The profiles of 21,757 miRNAs in the Atlas were highly consistent with those of plant miRNAs in miRBase. Using software tools, our results demonstrated that all human genes might be regulated by sRNAs from the Bencao sRNA Atlas, part of the predicted human target genes were experimentally validated, suggesting that Bencao sRNAs might be one of the main bioactive components of herbal medicines. We established roadmaps for oligonucleotide drugs development and optimization of TCM prescriptions. Moreover, the decoctosome, a lipo-nano particle consisting of 0.5%-2.5% of the decoction, demonstrated potent medical effects. We propose a Bencao (herbal) Index, including small-molecule compounds (SM), protein peptides (P), nucleic acid (N), non-nucleic and non-proteinogenic large-molecule compounds (LM) and elements from Mendeleev's periodic table (E), to quantitatively measure the medical effects of botanic medicine. The Bencao sRNA Atlas is a resource for developing gene-targeting oligonucleotide drugs and optimizing botanical medicine, and may provide potential remedies for the theory and practice of one medicine.

Avian influenza viruses suppress innate immunity by inducing trans-transcriptional readthrough via SSU72.

Innate immunity plays critical antiviral roles. The highly virulent avian influenza viruses (AIVs) H5N1, H7N9, and H5N6 can better escape host innate immune responses than the less virulent seasonal H1N1 virus. Here, we report a mechanism by which transcriptional readthrough (TRT)-mediated suppression of innate immunity occurs post AIV infection. By using cell lines, mouse lungs, and patient PBMCs, we showed that genes on the complementary strand ("trans" genes) influenced by TRT were involved in the disruption of host antiviral responses during AIV infection. The trans-TRT enhanced viral lethality, and TRT abolishment increased cell viability and STAT1/2 expression. The viral NS1 protein directly bound to SSU72, and degradation of SSU72 induced TRT. SSU72 overexpression reduced TRT and alleviated mouse lung injury. Our results suggest that AIVs infection induce TRT by reducing SSU72 expression, thereby impairing host immune responses, a molecular mechanism acting through the NS1-SSU72-trans-TRT-STAT1/2 axis. Thus, restoration of SSU72 expression might be a potential strategy for preventing AIV pandemics.

Neutrophil Gelatinase-Associated Lipocalin Contributes to Increased Risk of Cardiovascular Death After Acute Coronary Syndrome.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) has been suggested to reflect early renal dysfunction. We investigated the predictive significance of serum NGAL in predicting cardiovascular (CV) death in an old-age population with coronary heart disease (CHD). METHODS: In total, 633 CHD patients with a stable clinical condition were enrolled. The measurements of serum NGAL and other laboratory indices were performed within 24 hours after admission. Adjusted analysis was used to assess relationships between serum NGAL and CV death during the 10-year follow-up period. RESULTS: Multivariate logistic regression analysis demonstrated that elevated NGAL levels were related to a higher prevalence of CV disease history [quartile 4, 2.41 (1.60-4.59), P-trend <0.001]. The Kaplan-Meier curve indicated that patients with high NGAL levels tended to have a higher rate of CV death than patients with low NGAL levels. A multivariate Cox model suggested that increased levels of NGAL were independently linked with elevated risk of CV death (HR=2.62, 95% CI 1.51-4.96, P<0.001) during the 10-year follow-up period, after adjusting for related confounding factors using sensitivity analysis. Furthermore, the receiver operating characteristics (ROC) curve demonstrated that serum NGAL (AUC=0.917, 95% CI 0.895-0.940, P<0.001) had an ideal predictive value in predicting CV death. CONCLUSION: Serum levels of NGAL were elevated in patients with CHD and may be a new parameter that could independently predict CV death in these patients, which may strengthen its potential application in clinical practice.

Association between short-term exposure to air pollution and COVID-19 infection: Evidence from China.

The novel coronavirus pneumonia, namely COVID-19, has become a global public health problem. Previous studies have found that air pollution is a risk factor for respiratory infection by carrying microorganisms and affecting body's immunity. This study aimed to explore the relationship between ambient air pollutants and the infection caused by the novel coronavirus. Daily confirmed cases, air pollution concentration and meteorological variables in 120 cities were obtained from January 23, 2020 to February 29, 2020 in China. We applied a generalized additive model to investigate the associations of six air pollutants (PM2.5, PM10, SO2, CO, NO2 and O3) with COVID-19 confirmed cases. We observed significantly positive associations of PM2.5, PM10, NO2 and O3 in the last two weeks with newly COVID-19 confirmed cases. A 10-µg/m3 increase (lag0-14) in PM2.5, PM10, NO2, and O3 was associated with a 2.24% (95% CI: 1.02 to 3.46), 1.76% (95% CI: 0.89 to 2.63), 6.94% (95% CI: 2.38 to 11.51), and 4.76% (95% CI: 1.99 to 7.52) increase in the daily counts of confirmed cases, respectively. However, a 10-µg/m3 increase (lag0-14) in SO2 was associated with a 7.79% decrease (95% CI: -14.57 to -1.01) in COVID-19 confirmed cases. Our results indicate that there is a significant relationship between air pollution and COVID-19 infection, which could partially explain the effect of national lockdown and provide implications for the control and prevention of this novel disease.

Association between extreme heat and hospital admissions for cataract patients in Hefei, China.

Cataract is the first cause of blindness and the major cause of visual impairment worldwide. Under conditions of global warming, researchers have begun to give attention to the influence of increasing temperature on cataract patients. Our paper aimed to investigate the association between extreme heat and hospital admissions for cataract in Hefei, China. Based on data from the New Rural Cooperative Medical System and National Meteorological Information Center, we used a generalized additive model and a distributed lag nonlinear model to examine the relationship between extreme heat and hospitalizations for cataract, with consideration of cumulative and lagged effects. When current mean temperature was above 28 °C, each 1 °C rise was associated with a 4% decrease in the number of cataract admissions (RR = 0.96, 95% CI = 0.94-0.98). The cumulative relative risk over 11 days of lag was the lowest, which indicated that every 1 °C increase in mean temperature above 28 °C was associated with a 19% decrease in the number of hospital admissions for cataract (RR = 0.81, 95% CI = 0.75-0.88). In subgroup analyses, the negative association between extreme heat and hospital admissions for cataract was stronger among patients who were not admitted to provincial-level hospitals. In conclusion, this paper found that extreme heat was negatively associated with cataract hospitalizations in Hefei, providing useful information for hospitals and policymakers.

Chemical Cues Induced from Fly-Oviposition Mediate the Host-Seeking Behaviour of Fopius arisanus (Hymenoptera: Braconidae), an Effective Egg Parasitoid of Bactrocera dorsalis (Diptera: Tephritidae), within a Tritrophic Context.

Fopius arisanus is a solitary endoparasitoid that parasitizes a variety of tephritid species. Native to the Indo-Australian region, it is currently exploited worldwide as a biological control agent due to its exceptional efficiency in reducing pest populations. The efficiency of any biological control program is affected by the host location ability of the parasitoids. The present study used a Y-tube olfactometer to test the behavioural responses of female F. arisanus to four fruit species which had undergone different types of damages: undamaged, damaged through Bactrocera dorsalis ovipositioning (i.e., infested), or different levels of mechanical damage. Our results suggest that F. arisanus females were significantly attracted to mangoes and pears (vs. purified air), regardless of their condition; however, whilst infested mangoes did not attract more female parasitoids compared to healthy or mechanically damaged fruits, infested pears attracted significantly more. For citrus fruits and peaches, oviposition damage caused them to be more attractive to parasitoid females. In terms of the longevity of the effects, infested mango fruits remained attractive for up to 5 days after infestation, whereas for infested peaches, pears, and citrus fruits, the attractiveness tended to decrease as time passed. Regarding mechanical damage, mango fruits that had undergone any intensity of damage were equally attractive to parasitoid females; however, peach and citrus fruits with high levels of mechanical damage were more attractive, and pears were found to be most attractive with slight mechanical damage. Additional to the above, we also tested the effect of insecticides on behavioural responses using mangoes. We found that the treatment of infested fruits with lambda-cyhalothrin and cypermethrin remained attractive to F. arisanus females, albeit to different extents, which is in contrast to spinosad, cyantraniliprole, and acetamiprid. Finally, we suggest that the host-searching behaviour of F. arisanus females is mainly mediated by oviposition-induced volatiles, either emitted from the fruit or left by the fruit fly.

Antihypertensive drugs are associated with reduced fatal outcomes and improved clinical characteristics in elderly COVID-19 patients.

The novel coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 outbreak began at the end of 2019 in Wuhan, China, and has spread to over 200 countries. In this multicenter retrospective study, we identified 2190 adult patients admitted for laboratory-confirmed COVID-19 in three participating centers. Multivariate logistic regression was conducted in patients with comorbid hypertension to examine the potential association between clinical outcomes, disease severity, and clinical characteristics with the use of ACEI, ARB, calcium-channel blockers (CCB), beta-blockers (BB), and thiazide diuretics. The clinical outcome, dyspnea, and fatigue were significantly improved in patients, especially elderly patients who were older than 65 years, who took ARB drugs prior to hospitalization compared to patients who took no drugs. The reduction of disease severity of elderly COVID-19 patients was associated with CCB and ACEI users. Clinical indices, including CRP, lymphocyte count, procalcitonin D dimer, and hemoglobin, were significantly improved in elderly ARB users. In addition, the clinical outcomes were statistically significantly improved in patients who took antihypertension drugs ARB, BB, and CCB after statistical adjustment by all ages, gender, baseline of blood pressures, and coexisting medical conditions. Our data indicate that hypertension drugs ARB, ACEI, CCB, and BB might be beneficial for COVID-19 patients.