Postextrasystolic repolarization changes of ventricular premature beats correlate with structural heart disease and suggest prognostic implications.

Ventricular premature beats (VPBs) can potentially lead to life-threatening arrhythmias, especially in patients with structural heart disease (SHD). However, identifying dangerous VPBs has always been a topic and challenge in clinical research. This study aimed to evaluate the relationship of postextrasystolic repolarization changes of VPBs with SHD and its possible additional prognostic value. 125 cases of frequent VPBs with SHD and 156 cases without SHD were included. VPBs were stratified selected from 24 h Holter recording according to the scale of heart rate. Average QTDV (difference value of QT interval between the first beat follow VPB with beats preceding VPB) and max QTDV were significantly longer in SHD group than that in the non-SHD group. For identifying patients with SHD, the best cutoff value were 19 ms for average QTDV (AUC = 0.931) and 29 ms for max QTDV (AUC = 0.910) respectively. For Tu morphology analysis, PT2 (postextrasystolic T wave amplitude change ≥2 mV), reversed T wave, and Pu (postextrasystolic u wave) change were all highly specific, but low sensitive as identification of SHD. Compared with average QTDV < 19 ms patients, average QTDV ≥ 19 ms patients had significantly larger left heart size and wores left cardiac function. The presence of non-persistent ventricular tachycardia runs was higher in average QTDV ≥ 19 ms group and positive Pu change group than that in control groups. The findings indicated that postextrasystolic repolarization changes of VPBs correlated with SHD and suggested potential value in prognosis asssessment.

An Innovative Approach to Alleviate Zinc Oxide Nanoparticle Stress on Wheat through Nanobubble Irrigation.

The extensive utilization of zinc oxide nanoparticles in consumer products and the industry has led to their substantial entry into the soil through air and surface runoff transportation, which causes ecotoxicity in agro-ecosystems and detrimental effects on crop production. Nanobubbles (diameter size < 1 µm) have many advantages, such as a high surface area, rapid mass transfer, and long retention time. In this study, wheat seedlings were irrigated with a 500 mg L-1 zinc oxide nanoparticle solution delivered in the form of nanobubble watering (nanobubble-ZnO-NPs). We found that nanobubble watering improved the growth and nutrient status of wheat exposed to zinc oxide nanoparticles, as evidenced by increased total foliar nitrogen and phosphorus, along with enhanced leaf dry mass per area. This effect can be attributed to nanobubbles disassembling zinc oxide aggregates formed due to soil organic carbon, thereby mitigating nutrient absorption limitations in plants. Furthermore, nanobubbles improved the capability of soil oxygen input, leading to increased root activity and glycolysis efficiency in wheat roots. This work provides valuable insights into the influence of nanobubble watering on soil quality and crop production and offers an innovative approach for agricultural irrigation that enhances the effectiveness and efficiency of water application.

Efficacy and safety of tenofovir disoproxil fumarate versus entecavir in the treatment of acute-on-chronic liver failure with hepatitis B: a systematic review and meta-analysis.

BACKGROUND: Oral nucleoside (acid) analogues (NAs) are recommended for patients with acute-on-chronic liver failure (ACLF) associated with hepatitis B virus (HBV-ACLF). The efficacy and safety of tenofovir (TDF) and entecavir (ETV) in these patients remain unclear. METHODS: A comprehensive literature search in PubMed, Web of Science, The Cochrane Library, and Embase database was conducted to select studies published before December 2022 on TDF or ETV for HBV-ACLF. The primary outcomes were survival rates at 4, 12, and 48 weeks. Secondary outcomes were virologic and biochemical responses, serum antigen conversion, liver function score, and safety. RESULTS: Four prospective and one retrospective cohort studies were selected. The overall analysis showed comparable survival rates at 4, 12, and 48 weeks for all patients receiving TDF or ETV (4-week: RR = 1.17, 95% CI: 0.90-1.51, p = 0.24; 12-week: RR = 1.00, 95% CI: 0.88-1.13, p = 0.94; 48-week: RR = 0.96, 95% CI: 0.58-1.57, p = 0.86). Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) score at 12 weeks were comparable in both groups but lower than baseline (CTP: SMD = -0.75, 95% CI:-2.81-1.30, p = 0.47; MELD: SMD = -1.10, 95% CI:-2.29-0.08, p = 0.07). At 48 weeks, estimated glomerular filtration rate (eGFR) levels were found to decrease to different degrees from baseline in both the TDF and ETV groups, and the decrease was greater in the TDF group than in the ETV group. No significant differences were found in biochemical, virologic response, and serum antigen conversion between the two groups during the observation period. CONCLUSION: TDF treatment of HBV-ACLF is similar to ETV in improving survival, liver function, and virologic response but the effects on renal function in two groups in the long term remain unclear. More and larger long-term clinical trials are required to confirm these findings.

MRSA-induced endothelial permeability and acute lung injury are attenuated by FTY720 S-phosphonate.

Disruption of the lung endothelial barrier is a hallmark of acute respiratory distress syndrome (ARDS), for which no effective pharmacologic treatments exist. Prior work has demonstrated that FTY720 S-phosphonate (Tys), an analog of sphingosine-1-phosphate (S1P) and FTY720, exhibits potent endothelial cell (EC) barrier protective properties. In this study, we investigated the in vitro and in vivo efficacy of Tys against methicillin-resistant Staphylococcus aureus (MRSA), a frequent bacterial cause of ARDS. Tys-protected human lung EC from barrier disruption induced by heat-killed MRSA (HK-MRSA) or staphylococcal α-toxin and attenuated MRSA-induced cytoskeletal changes associated with barrier disruption, including actin stress fiber formation and loss of peripheral VE-cadherin and cortactin. Tys-inhibited Rho and myosin light chain (MLC) activation after MRSA and blocked MRSA-induced NF-κB activation and release of the proinflammatory cytokines, IL-6 and IL-8. In vivo, intratracheal administration of live MRSA in mice caused significant vascular leakage and leukocyte infiltration into the alveolar space. Pre- or posttreatment with Tys attenuated MRSA-induced lung permeability and levels of alveolar neutrophils. Posttreatment with Tys significantly reduced levels of bronchoalveolar lavage (BAL) VCAM-1 and plasma IL-6 and KC induced by MRSA. Dynamic intravital imaging of mouse lungs demonstrated Tys attenuation of HK-MRSA-induced interstitial edema and neutrophil infiltration into lung tissue. Tys did not directly inhibit MRSA growth or viability in vitro. In conclusion, Tys inhibits lung EC barrier disruption and proinflammatory signaling induced by MRSA in vitro and attenuates acute lung injury induced by MRSA in vivo. These results support the potential utility of Tys as a novel ARDS therapeutic strategy.

A HSV1 mutant leads to an attenuated phenotype and induces immunity with a protective effect.

Herpes simplex virus type 1 (HSV1) is a complicated structural agent with a sophisticated transcription process and a high infection rate. A vaccine against HSV1 is urgently needed. As multiple viral-encoded proteins, including structural and nonstructural proteins, contribute to immune response stimulation, an attenuated or deficient HSV1 vaccine may be relatively reliable. Advances in genomic modification technologies provide reliable means of constructing various HSV vaccine candidates. Based on our previous work, an M6 mutant with mutations in the UL7, UL41, LAT, Us3, Us11 and Us12 genes was established. The mutant exhibited low proliferation in cells and an attenuated phenotype in an animal model. Furthermore, in mice and rhesus monkeys, the mutant can induce remarkable serum neutralizing antibody titers and T cell activation and protect against HSV1 challenge by impeding viral replication, dissemination and pathogenesis.

Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression.

The COVID-19 has emerged as an epidemic, causing severe pneumonia with a high infection rate globally. To better understand the pathogenesis caused by SARS-CoV-2, we developed a rhesus macaque model to mimic natural infection via the nasal route, resulting in the SARS-CoV-2 virus shedding in the nose and stool up to 27 days. Importantly, we observed the pathological progression of marked interstitial pneumonia in the infected animals on 5-7 dpi, with virus dissemination widely occurring in the lower respiratory tract and lymph nodes, and viral RNA was consistently detected from 5 to 21 dpi. During the infection period, the kinetics response of T cells was revealed to contribute to COVID-19 progression. Our findings implied that the antiviral response of T cells was suppressed after 3 days post infection, which might be related to increases in the Treg cell population in PBMCs. Moreover, two waves of the enhanced production of cytokines (TGF-α, IL-4, IL-6, GM-CSF, IL-10, IL-15, IL-1ß), chemokines (MCP-1/CCL2, IL-8/CXCL8, and MIP-1ß/CCL4) were detected in lung tissue. Our data collected from this model suggested that T cell response and cytokine/chemokine changes in lung should be considered as evaluation parameters for COVID-19 treatment and vaccine development, besides of observation of virus shedding and pathological analysis.

Randomized, Double-Blinded, Placebo-Controlled Phase 2 Trial of an Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in Healthy Adults.

BACKGROUND: We evaluated an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine for immunogenicity and safety in adults aged 18-59 years. METHODS: In this randomized, double-blinded, controlled trial, healthy adults received a medium dose (MD) or a high dose (HD) of the vaccine at an interval of either 14 days or 28 days. Neutralizing antibody (NAb) and anti-S and anti-N antibodies were detected at different times, and adverse reactions were monitored for 28 days after full immunization. RESULTS: A total of 742 adults were enrolled in the immunogenicity and safety analysis. Among subjects in the 0, 14 procedure, the seroconversion rates of NAb in MD and HD groups were 89% and 96% with geometric mean titers (GMTs) of 23 and 30, respectively, at day 14 and 92% and 96% with GMTs of 19 and 21, respectively, at day 28 after immunization. Anti-S antibodies had GMTs of 1883 and 2370 in the MD group and 2295 and 2432 in the HD group. Anti-N antibodies had GMTs of 387 and 434 in the MD group and 342 and 380 in the HD group. Among subjects in the 0, 28 procedure, seroconversion rates for NAb at both doses were both 95% with GMTs of 19 at day 28 after immunization. Anti-S antibodies had GMTs of 937 and 929 for the MD and HD groups, and anti-N antibodies had GMTs of 570 and 494 for the MD and HD groups, respectively. No serious adverse events were observed during the study period. CONCLUSIONS: Adults vaccinated with inactivated SARS-CoV-2 vaccine had NAb as well as anti-S/N antibody and had a low rate of adverse reactions. CLINICAL TRIALS REGISTRATION: NCT04412538.

Emodin inhibits aggregation of amyloid-ß peptide 1-42 and improves cognitive deficits in Alzheimer's disease transgenic mice.

Aggregation of amyloid-ß peptide 1-42 (Aß42) initiates the onset of Alzheimer's disease (AD), and all the drugs designed to attenuate AD have failed in clinical trials. Emodin reduces levels of ß-amyloid, tau aggregation, oxidative stress, and inflammatory response, demonstrating AD therapeutic potential, whereas its effect on the accumulation of the amyloid-ß protein is not well understood. In this work, we investigated emodin activity on Aß aggregation using a range of biochemical, biophysical, and cell-based approaches. We provide evidence to suggest that emodin blocks Aß42 fibrillogenesis and Aß-induced cytotoxicity, displaying a greater effect than that of curcumin. Through adopting three short peptides (Aß1-16, Aß17-33, and Aß28-42), it was proven that emodin interacts with the Leu17-Gly33 sequence. Furthermore, our findings indicated that Val18 and Phe19 in Aß42 are the target residues with which emodin interacts according amino acid mutation experiments. When fed to 8-month-old B6C3-Tg mice for 2 months, high-dose emodin ameliorates cognitive impairment by 60%-70%. Pathological results revealed that levels of Aß deposition in the brains of AD mice treated with a high dose of emodin decreased by 50%-70%. Therefore, our study indicates that emodin may represent a promising drug for AD treatment.

SARS-CoV-2 S1 is superior to the RBD as a COVID-19 subunit vaccine antigen.

Since its emergence in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global pandemic within a matter of months. While subunit vaccines are one of the prominent options for combating coronavirus disease 2019 (COVID-19), the immunogenicity of spike protein-based antigens remains unknown. When immunized in mice, the S1 domain induced much higher IgG and IgA antibody levels than the receptor-binding domain (RBD) and more efficiently neutralized SARS-CoV-2 when adjuvanted with alum. It is inferred that a large proportion of these neutralization epitopes are located in the S1 domain but outside the RBD and that some of these are spatial epitopes. This finding indicates that expression systems with posttranslational modification abilities are important to maintain the natural configurations of recombinant spike protein antigens and are critical for effective COVID-19 vaccines. Further, adjuvants prone to a Th1 response should be considered for S1-based subunit COVID-19 vaccines to reduce the potential risk of antibody-dependent enhancement of infection.

Serum levels of irisin in postmenopausal women with osteoporotic hip fractures.

OBJECTIVE: The purpose of this study was to evaluate the role of circulating serum levels of irisin in predicting hip fracture occurrence in a cohort of Chinese postmenopausal women. METHODS: This was a cross-section and case-control study. Four hundred and thirty postmenopausal women aged 50-90 years were included (215 with hip fractures and 215 age-matched cases without fracture). Clinical features, bone mineral density (BMD) and serum biomarkers levels including irisin were measured at baseline. Cox proportional hazards regression analysis was used to assess the correlation between irisin and fracture risk. RESULTS: The mean age of those participants was 68.7 (S.D. 11.7) and 53.0% were order than 65. The irisin serum levels were positively related to total body BMD and total hip BMD. Women with hip fractures showed lower mean serum levels of irisin compared normal control women (457.6 ± 172.6 ng/ml vs. 602.2 ng/ml; P < 0.001). The irisin levels in third and fourth quartiles were associated with the risk of hip fracture (the lowest quartile of irisin levels as the reference), and risk of fracture reduced by 67% (hazard ratio [HR] = 0.33; 95 %CI: 0.18-0.54; P < 0.001) and 84% (HR = 0.16; 95 %CI: 0.09-0.29; P < 0.001). The irisin levels in third and fourth quartiles were also associated with the risk of osteoporosis, and risk of fracture reduced by 55% (HR = 0.45; 95 %CI: 0.21-0.63; P = 0.003) and 73% (HR = 0.27; 95 %CI: 0.15-0.47; P < 0.001). CONCLUSION: Decreased serum levels of circulating irisin are associated with high risk of osteoporosis-related hip fractures and osteoporosis.

An electrographic AV optimization for the maximum integrative atrioventricular and ventricular resynchronization in CRT.

BACKGROUND: Atrioventricular (AV) delay could affect AV and ventricular synchrony in cardiac resynchronization therapy (CRT). Strategies to optimize AV delay according to optimal AV synchrony (AVopt-AV) or ventricular synchrony (AVopt-V) would potentially be discordant. This study aimed to explore a new AV delay optimization algorithm guided by electrograms to obtain the maximum integrative effects of AV and ventricular resynchronization (opt-AV). METHODS: Forty-nine patients with CRT were enrolled. AVopt-AV was measured through the Ritter method. AVopt-V was obtained by yielding the narrowest QRS. The opt-AV was considered to be AVopt-AV or AVopt-V when their difference was < 20 ms, and to be the AV delay with the maximal aortic velocity-time integral between AVopt-AV and AVopt-V when their difference was > 20 ms. RESULTS: The results showed that sensing/pacing AVopt-AV (SAVopt-AV/PAVopt-AV) were correlated with atrial activation time (Pend-As/Pend-Ap) (P < 0.05). Sensing/pacing AVopt-V (SAVopt-V/PAVopt-V) was correlated with the intrinsic AV conduction time (As-Vs/Ap-Vs) (P < 0.01). The percentages of patients with more than 20 ms differences between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were 62.9% and 57.1%, respectively. Among them, opt-AV was linearly correlated with SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The sensing opt-AV (opt-SAV) = 0.1 × SAVopt-AV + 0.4 × SAVopt-V + 70 ms (R2 = 0.665, P < 0.01) and the pacing opt-AV (opt-PAV) = 0.25 × PAVopt-AV + 0.5 × PAVopt-V + 30 ms (R2 = 0.560, P < 0.01). CONCLUSION: The SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were correlated with the atrial activation time and the intrinsic AV conduction interval respectively. Almost half of the patients had a > 20 ms difference between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The opt-AV could be estimated based on electrogram parameters.

Electrophysiological characteristics of epicardial to endocardial breakthrough in intractable cavotricuspid isthmus-dependent atrial flutter.

BACKGROUND: Epicardial to endocardial breakthrough (EEB) exists widely in atrial arrhythmia and is a cause for intractable cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL). This study aimed to investigate the electrophysiological features of EEB in EEB-related CTI dependent AFL. METHODS: Six patients with EEB-related CTI-dependent AFL were identified among 142 consecutive patients who underwent CTI-dependent AFL catheter ablation with an ultra-high-density, high-resolution mapping system in three institutions. Activation maps and ablation procedure were analyzed. RESULTS: A total of seven EEBs were found in six patients. Four EEBs (including three at the right atrial septum and one in paraseptal isthmus) were recorded in three patients during tachycardia. The other three EEBs were identified at the inferolateral right atrium (RA) during pacing from the coronary sinus. The conduction characteristics through the EEB-mediated structures were evaluated in three patients. Two patients only showed unidirectional conduction. Activation maps indicated that CTI-dependent AFL with EEB at the atrial septum was actually bi-atrial macro-reentrant atrial tachycardia (BiAT). Intensive ablation at the central isthmus could block CTI bidirectionally in four cases. However, ablation targeted at the inferolateral RA EEB was required in two cases. Meanwhile, local potentials at the EEB location gradually split into two components with a change in activation sequence. CONCLUSIONS: EEB is an underlying cause for intractable CTI-dependent AFL. EEB-mediated structure might show unidirectional conduction. CTI-dependent AFL with EEB at the atrial septum may represent BiAT. Intensive ablation targeting the central isthmus or EEB at the inferolateral RA could block the CTI bidirectionally.

Effects of the intermediate care unit on the oldest-old general surgical patients: a retrospective, pre- and postintervention study.

BACKGROUND: Whether the intermediate care unit (IMCU) is beneficial for the oldest-old (aged ≥ 80 years) general surgical patients still remains unknown. We aimed to investigate the impacts of IMCU on the clinical outcomes and cost in this population. METHODS: A retrospective, pre- and postintervention study was performed in this population in a university teaching hospital. The primary outcome was the occurrence of life-threatening complications including death or unplanned ICU admission after the surgeries. Secondary outcomes included the comparisons of the hospitalization expenses, the hospital length of stay (LOS) and the postoperative LOS between the pre-IMCU group and the IMCU group. RESULTS: Two hundred and seventeen patients were enrolled, including 98 in the pre-IMCU group and 119 in the IMCU group. After the introduction of IMCU, the occurrence of life-threatening complications significantly dropped from 11.2 to 2.5% (P = 0.012). The total hospitalization expenses showed a nonsignificant decreasing trend in the IMCU group (pre-IMCU group: 85856.3 ± 66583.7 RMB vs IMCU group: 78936.4 ± 36710.4 RMB). The treatment fee was much lower in the IMCU group (IMCU group: 4930.0 ± 4280.2 RMB vs pre-IMCU group: 7378.2 ± 10096.7 RMB, P = 0.017). Both the hospital LOS (IMCU group: 20.3 ± 10.3 days vs pre-IMCU group: 19.5 ± 9.0 days) and the postoperative hospital LOS (IMCU group: 12.0 ± 8.1 days vs pre-IMCU group: 11.2 ± 7.0 days) were not statistically different in the two groups. CONCLUSIONS: The allocation of the oldest-old surgical patients who do not need organ support therapy in the ICU to IMCU rather than in the standard wards was associated with a significant decrease in postoperative life-threatening complications and treatment fee. TRIAL REGISTRATION: This study was registered at https://www.chictr.org.cn (ChiCTR2000030639).

A Wrist Sensor Sleep Posture Monitoring System: An Automatic Labeling Approach.

In the hospital, a sleep postures monitoring system is usually adopted to transform sensing signals into sleep behaviors. However, a home-care sleep posture monitoring system needs to be user friendly. In this paper, we present iSleePost-a user-friendly home-care intelligent sleep posture monitoring system. We address the labor-intensive labeling issue of traditional machine learning approaches in the training phase. Our proposed mobile health (mHealth) system leverages the communications and computation capabilities of mobile phones for provisioning a continuous sleep posture monitoring service. Our experiments show that iSleePost can achieve up to 85 percent accuracy in recognizing sleep postures. More importantly, iSleePost demonstrates that an easy-to-wear wrist sensor can accurately quantify sleep postures after our designed training phase. It is our hope that the design concept of iSleePost can shed some lights on quantifying human sleep postures in the future.

Silence Is Golden.

Speech-induced atrial tachycardia (AT) is extremely rare. We presented a case of focal AT that could be triggered by speech and terminated with the cessation of conversation. An electrophysiological study showed that the outbreak was associated with left atrial pressure rose. Radiofrequency ablation at the left atrial posterior-superior wall (earliest activation site) resulted in the immediate termination of AT. These electrophysiological characteristics indicated that the cardiac autonomic nervous system and/or left atrial pressure might play essential roles in the occurrences of speech-induced AT.

Can drip irrigation under mulch be replaced with shallow-buried drip irrigation in spring maize production systems in semiarid areas of northern China?

BACKGROUND: In recent years, shallow-buried drip irrigation in spring maize production has gradually replaced drip irrigation under plastic films and has become a common irrigation method in semiarid areas of northern China. RESULT: Two years of field experiments were carried out in the semiarid area of western Jilin province to compare the two drip irrigation methods in the spring maize production system. The treatments included MW1 (drip irrigation under mulch + moderate irrigation amount), MW2 (drip irrigation under mulch + high irrigation amount), SM1 (shallow-buried drip irrigation + moderate irrigation amount), and SM2 (shallow-buried drip irrigation + high irrigation amount). The maize yields were significantly higher under mulch than under shallow-buried drip irrigation, but there was no interaction between mulch and the irrigation amount. Drip irrigation under mulch greatly improved spring maize N, P and K uptake compared with that under shallow-buried drip irrigation. The agronomic-use efficiency, recovery-use efficiency, and partial factor productivity were ranked in the order of MW2 > MW1 > SW2 > SW1. The water-use efficiency of drip irrigation under mulch was 7.44% and 6.82% higher than that of shallow-buried drip irrigation under the moderate and high irrigation levels, respectively. However, considering the costs of the plastic mulch, there was no significant (P < 0.05) difference in economic benefits between the SW and MW treatments. CONCLUSION: Drip irrigation under plastic film provides greater advantages for production, but shallow-buried drip irrigation may be a suitable method for farmers until fertigation technology is further optimized and the problem of plastic film pollution is solved. © 2020 Society of Chemical Industry.

Dynamics of NK, CD8 and Tfh cell mediated the production of cytokines and antiviral antibodies in Chinese patients with moderate COVID-19.

Recent studies have demonstrated a marked decrease in peripheral lymphocyte levels in patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Few studies have focused on the changes of NK, T- and B-cell subsets, inflammatory cytokines and virus-specific antibodies in patients with moderate COVID-19. A total of 11 RT-PCR-confirmed convalescent patients with COVID-19 and 11 patients with non-SARS-CoV-2 pneumonia (control patients) were enrolled in this study. NK, CD8+ T, CD4+ T, Tfh-like and B-cell subsets were analysed using flow cytometry. Cytokines and SARS-CoV-2-specific antibodies were analysed using an electrochemiluminescence immunoassay. NK cell counts were significantly higher in patients with COVID-19 than in control patients (P = 0.017). Effector memory CD8+ T-cell counts significantly increased in patients with COVID-19 during a convalescent period of 1 week (P = 0.041). TIM-3+ Tfh-like cell and CD226+ Tfh-like cell counts significantly increased (P = 0.027) and decreased (P = 0.022), respectively, during the same period. Moreover, ICOS+ Tfh-like cell counts tended to decrease (P = 0.074). No abnormal increase in cytokine levels was observed. The high expression of NK cells is important in innate immune response against SARS-CoV-2. The increase in effector memory CD8+ T-cell counts, the up-regulation of inhibitory molecules and the down-regulation of active molecules on CD4+ T cells and Tfh-like cells in patients with COVID-19 would benefit the maintenance of balanced cellular and humoural immune responses, may prevent the development of severe cases and contribute to the recovery of patients with COVID-19.

Mechanism for the lethal effect of enterovirus A71 intracerebral injection in neonatal mice.

Enterovirus A71 (EV-A71) infection is primarily responsible for fatal hand, foot, and mouth disease (HFMD) cases. Infants and younger children are more likely to suffer central nervous system damage as a result of EV-A71 infection, but this virus mostly does not affect older children and adults. This study investigated the possible mechanism underlying the age-dependent lethal effect of EV-A71 infection by comparing neonatal and adult mouse models of EV-A71 infection. Although viral proliferation is absent in both neonatal and adult mice, we observed that EV-A71, as a stimulus for astrocytes, elevates the levels of cytokines and monoamine neurotransmitters in neonatal mice. Then, we selected IL-6 and adrenaline as targets in a pharmacological approach to further validate the roles of these factors in mediating the mortality of neonatal mice after EV-A71 infection. Intracerebral injection of IL-6 and adrenaline enhanced the severity of EV-A71 infection, while treatment with an anti-IL-6-neutralizing antibody or the adrenergic-antagonist phenoxybenzamine reversed the lethal effect of EV-A71 in neonatal mice. These results suggest that the central nervous system (CNS) damage in neonatal cases of EV-A71 infection might be caused by an activated fetal cerebral immune response to the virus, including the disruption of brainstem function through increased levels of cytokines and neurotransmitters, rather than the typical cytopathic effect (CPE) of viral infection.

Distinct infection process of SARS-CoV-2 in human bronchial epithelial cell lines.

Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leads to a series of clinical symptoms of respiratory and pulmonary inflammatory reactions via unknown pathologic mechanisms related to the viral infection process in tracheal or bronchial epithelial cells. Investigation of this viral infection in the human bronchial epithelial cell line (16HBE) suggests that SARS-CoV-2 can enter these cells through interaction between its membrane-localized S protein with the angiotensin-converting enzyme 2 molecule on the host cell membrane. Further observation indicates distinct viral replication with a dynamic and moderate increase, whereby viral replication does not lead to a specific cytopathic effect but maintains a continuous release of progeny virions from infected cells. Although messenger RNA expression of various innate immune signaling molecules is altered in the cells, transcription of interferons-α (IFN-α), IFN-ß, and IFN-γ is unchanged. Furthermore, expression of some interleukins (IL) related to inflammatory reactions, such as IL-6, IL-2, and IL-8, is maintained at low levels, whereas that of ILs involved in immune regulation is upregulated. Interestingly, IL-22, an IL that functions mainly in tissue repair, shows very high expression. Collectively, these data suggest a distinct infection process for this virus in respiratory epithelial cells, which may be linked to its clinicopathological mechanism.

Magnesium accumulation, partitioning and remobilization in spring maize (Zea mays L.) under magnesium supply with straw return in northeast China.

BACKGROUND: Magnesium (Mg) has important effects on maize growth, and the application of Mg fertilizer with straw return inevitably has an impact on Mg absorption in maize. RESULTS: A two-year field trial was conducted to investigate the effects of Mg fertilizers with straw return on Mg accumulations, partitioning and remobilization in maize (Zea mays L.) in northeast China. The treatments included: (i) JM3 (straw + Mg fertilizer), (ii) JM0 (straw + no Mg fertilizer), (iii) WM3 (no straw + Mg fertilizer), and (iv) WM0 (no Mg fertilizer + no straw). The results showed that the highest Mg accumulation stage in maize was prominent between the tasseling stage (VT) and blister stage (R2), and JM3 treatment accumulated 13.3% and 26.6% more Mg on average than those of the WM3 and WM0, respectively. Magnesium remobilization in distinct organs was highest in JM3 and there were significant differences between treatments. The total contribution to the grain for the JM3 treatment was higher by 6.0% and 17.9% on average than those for the WM3 and WM0, respectively. The grain yield of JM3 treatment was 0.5% and 5.3% higher than that of WM3 and WM0, respectively. CONCLUSION: Generally, these outcomes indicated that there was an interaction between Mg fertilizer and maize straw. The application of Mg fertilizer significantly promoted the accumulation, distribution to the maize organs, and the remobilization of Mg. The combination of straw return and Mg application further increased the accumulation of Mg in the grain. And all these lead to an increase in yield. © 2020 Society of Chemical Industry.