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ZrO2 and catalysts were prepared by a co-precipitate method and coupled with a HZSM-5 zeolite catalyst through a mechanical mixing method; these were applied to the direct synthesis of aromatic hydrocarbons from syngas through an oxygen-containing intermediate route. The physical and chemical properties of the catalysts were characterized by XRD, H2-TPR, CO2-TPD, and SEM methods. The comparative catalytic effects of ZrO2 and MgZrOx catalysts were discussed under different reaction conditions. The reaction results showed that the addition of Mg to a ZrO2 catalyst reduced the selectivity of CO2 by inhibiting the water–gas conversion reaction, and increased the selectivity of aromatics and the proportion of BTX in aromatic products.

High-molecular-weight glutenin subunits (HMW-GS) contribute to dough elasticity and bread baking quality in wheat. In this study, wheat varieties were classified based on their HMW-GS composition into three groups: 1Dx5 (5 + 10, Gaoyou 8901, Xinmai 28, Xinmai 19, Xinmai 26 and Jinbaoyin), 1Dx2 (2 + 12, Zhoumai 24, Xinmai 9 and Yumai) and 1Dx4 (4 + 12, Aikang 58). Sequence analysis showed that 1Dx-GY8901, 1Dx-XM28, 1Dx-XM19 and 1Dx-XM26 were similar to the 1Dx5 gene and clustered on the same branch, while 1Dx-AK58, 1Dx-ZM24, 1Dx-JBY, 1Dx-YM, 1Dx-XM9 and 1Dx-JBY were more similar to the 1Dx2 gene and clustered on the same branch with 1Dx.2.2. There was a mutation of Ser to Cys at position S2, for an extra Cys in the repeat regions of 1Dx-XM19, 1Dx-XM26, 1Dx-XM28 and 1Dx-GY8901. The wheat HMW-GS genes exhibited similar percentages of α-helix, extended strand, β-turn and random coil structure, with ranges of 13.33–13.59, 4.77–5.78, 7.08–9.18 and 72.3–73.94%, respectively. Sequence conservation and the composition of HMW-GS subunits were also analysed for a series of strong gluten wheat varieties, Xinmai 9 (1, 7 + 8, 2 + 12), Xinmai 19 (1, 7 + 9, 5 + 10), Xinmai 26 (1, 7 + 8, 5 + 10) and Xinmai 28 (1, 7 + 9, 5 + 10). The results of this work should facilitate future breeding efforts and provide the theoretical basis for wheat quality improvement.

Tomato mottle mosaic virus (ToMMV) poses a threat to production and quality of tomato fruits. The Tm-22 gene confers resistance to some tobamoviruses by recognizing viral movement proteins. However, Tm-22-mediated resistance against ToMMV is not well known. Here, we found that ToMMV could infect wild-type but not Tm-22 transgenic Nicotiana benthamiana plants and could also infect tomato cultivar Moneymaker but not resistant cultivar Jili with homozygous Tm-22. Chimeric viral ToMMVToBRFV−MP with swapped ToMMV MP to MP of tomato brown rugose fruit virus could systemically infect Tm-22 transgenic N. benthamiana and tomato cultivars Jili plants. Further, transient expression of ToMMV MP in the leaves of Tm-22 transgenic N. benthamiana plants induced hypersensitive response-associated cell death, suggesting that the MP of ToMMV was the avirulent factor for the Tm-22 resistance gene. ToMMV could infect Tm-22-containing cultivar Jinpeng 1 but not Chaobei. Sequence analysis revealed that cultivars Chaobei and Jinpeng 1 were heterozygous, where Chaobei consists of Tm-22 and Tm-2 genes, while Jinpeng 1 consists of Tm-22 and tm-2 genes. Transient co-expression assays showed that both Tm-22 and Tm-2 but not tm-2 could recognize ToMMV MP and induce hypersensitivity response-associated cell death in N. benthamiana leaves, suggesting that homozygous tomato harboring Tm-22 and heterozygous tomato containing Tm-22 and Tm-2 may exhibit more durable resistance to ToMMV than heterozygous tomato carrying Tm-22 and tm-2. Further, Tm-22 transgenic N. benthamiana and tomato cultivar Jili plants with silenced Tm-22 gene were susceptible to ToMMV. Also, silencing type-I J-domain MIP1 gene compromised Tm-22-mediated resistance to ToMMV in Tm-22 transgenic N. benthamiana and tomato cultivar Jili. Moreover, we found that viral RNA could accumulate in the systemic leaves of Tm-22 transgenic N. benthamiana plants and tomato cultivar Jili at 35°C, but not at 20, 25, or 30°C. Altogether, our findings reveal that the Tm-22 confers resistance to ToMMV by recognizing MP, and the resistance is regulated by the allele combinations, accumulation levels of Tm-22, MIP1, and the temperature.

The high quility has become an important goal of wheat breeding. Several super-strong gluten wheat varieties, e.g. ‘Xinmai 26’ and ‘Xinmai 45’, have been bred to meet consumer market. However, the genetic composition, transmission frequency and genetic contribution of them and their progeny are not clear. To analyze the genetic composition of the high-quality strong gluten wheat varieties ‘Xinmai 26’ and ‘Xinmai 45’, the genetic contribution rates of male and female parents to the varieties were analyzed using 6056 SNP markers detected by a widely used high-throughput wheat array (15K chip). Additionally, the chromosome polymorphisms of five related wheat varieties were determined by fluorescence in situ hybridization (FISH) using four oligonucleotide probe sets. The results showed that the genetic contribution rate of ‘Jinan 17’ against ‘Xinmai 26’ was 55.97%, much higher than the 15.81% of ‘Xinmai 18’. ‘Jimai 20’ showed a genetic contribution rate of 57.53% against ‘Xinmai 45’, which was slightly higher than that of ‘Xinmai 26’ at 40.21%. The specific fragment differences from male and female parents were identified in both breeding varieties, and ‘Xinmai 26’ had more specific fragments that differed from male and female parents than ‘Xinmai 45’. The chromosomes of group A and group B of the five varieties were significantly polymorphic, but no chromosomes translocations or inversions were found. The promising results would be helpful to explore the genetic pattern of high-quality varieties, promote breeding efficiency, and utilize the superior traits of backbone parents for wheat quality improvement.

From the deep-sea-derived Fusarium sp. ZEN-48, four known compounds were obtained. Their structures were established by extensive analyses of the NMR, HR-ESI-MS, and the X-ray crystallographic data as brefeldin A (BFA, 1), brevianamide F (2), N-acetyltryptamine (3), and (+)-diaporthin (4). Although BFA was extensively investigated for its potent bioactivities, its role on TNFα-induced necroptosis was incompletely understood. In this study, BFA showed significant inhibition on TNFα-induced necroptosis by disrupting the necrosome formation and suppressing the phosphorylation of RIPK3 and MLKL (IC

Tomato cultivars containing the Tm-22 resistance gene have been widely known to resist tobacco mosaic virus (TMV) and tomato mosaic virus. Tomato brown rugose fruit virus (ToBRFV), a new emerging tobamovirus, can infect tomato plants carrying the Tm-22 gene. However, the virulence determinant of ToBRFV that overcomes the resistance conferred by the Tm-22 gene remains unclear. In this study, we substituted the movement protein (MP) encoding sequences between ToBRFV and TMV infectious clones and conducted infectivity assays. The results showed that MP was the virulence determinant for ToBRFV to infect Tm-22 transgenic Nicotiana benthamiana plants and Tm-22 -carrying tomato plants. A TMV MP chimera with amino acid residues 60-186 of ToBRFV MP failed to induce hypersensitive cell death in the leaves of Tm-22 transgenic N. benthamiana plants. Chimeric TMV containing residues 60-186 of ToBRFV MP could, but chimeric ToBRFV containing 61-187 residues of TMV MP failed to infect Tm-22 transgenic N. benthamiana plants, indicating that 60-186 residues of MP were important for ToBRFV to overcome Tm-22 gene-mediated resistance. Further analysis showed that six amino acid residues, H67 , N125 , K129 , A134 , I147 , and I168 of ToBRFV MP, were critical in overcoming Tm-22 -mediated resistance in transgenic N. benthamiana plants and tomato plants. These results increase our understanding of the mechanism by which ToBRFV overcomes Tm-22 -mediated resistance.

BACKGROUND Jejunal diverticula are the rarest of all small bowel diverticula and usually have no classic clinical symptoms. Jejunal diverticular haemorrhage (JDH) is a rare complication and can be difficult to identify and manage, hence it always resulting in a diagnostic delay and unsatisfactory clinical outcomes. Although with the advances in endoscopic technology, no consensus have been reached on the diagnosis and management of JDH, the conventional surgical intervention still remains the mainstream for the management of JDH. We report an unique case of a 63-year-old male who presented with massive haemorrhage from jejunal diverticula, which was successfully managed by initial resuscitation and definitive surgery. CASE SUMMARY A 63-year-old male was admitted as an emergency with 6 h history of haematemesis and melena. The haematemesis appeared to be bright red, with volume exceeding 100 mL. The amount of melena was estimated to be 200 mL. Initially, the patient received fluid resuscitation and three unit blood transfusion. Then, in order to localize the bleeding sites, colonoscopy, upper gastrointestinal endoscopy, and mesenteric angiography were utilized but failed to identify the source of haemorrhage. Informed consent form was obtained for further treatment, and he was treated with an exploratory laparotomy and the bleeding site was successfully located during the procedure. He was diagnosed with JDH. The postoperative period was uneventful, and he was discharged on day 18 after surgery. No rebleeding occurred at the 1-year follow-up. CONCLUSION In patients with gastrointestinal bleeding, if various techniques fail to identify the cause of haemorrhage in small bowel and haemodynamic instability is sustained with continuous resuscitation, we recommend surgical intervention should be the ultimate treatment of choice.

Tomato brown rugose fruit virus (ToBRFV) is a novel tobamovirus firstly reported in 2015 and poses a severe threat to the tomato industry. So far, it has spread to 10 countries in America, Asia, and Europe. In 2019, ToBRFV was identified in Shandong Province (ToBRFV-SD), China. In this study, it was shown that ToBRFV-SD induced mild to severe mosaic and blistering on leaves, necrosis on sepals and pedicles, and deformation, yellow spots, and brown rugose necrotic lesions on fruits. ToBRFV-SD induced distinct symptoms on plants of tomato, Capsicum annumm, and Nicotiana benthamiana, and caused latent infection on plants of Solanum tuberosum, Solanum melongena, and N. tabacum cv. Zhongyan 102. All the 50 tomato cultivars tested were highly sensitive to ToBRFV-SD. The complete genomic sequence of ToBRFV-SD shared the highest nucleotide and amino acid identities with isolate IL from Israel. In the phylogenetic tree constructed with the complete genomic sequence, all the ToBRFV isolates were clustered together and formed a sister branch with tobacco mosaic virus (TMV). Furthermore, a quadruplex RT-PCR system was developed that could differentiate ToBRFV from other economically important viruses affecting tomatoes, such as TMV, tomato mosaic virus, and tomato spotted wilt virus. The findings of this study enhance our understanding of the biological and molecular characteristics of ToBRFV and provide an efficient and effective detection method for multiple infections, which is helpful in the management of ToBRFV.

Background: The ‘risk criterion’ for involuntary admission (IA) has been adopted by Mental Health Law of the People’s Republic of China since 2013. How the new legal regulation influences daily practices in psychiatric institutes are still unclear. Aims: The present study sought to explore the application of risk criterion in IA cases; especially risk assessed by psychiatrists at admission and its influencing factors. Method: Socio-demographic and clinical data including risk assessment for admission of 3,529 involuntary admitted patients from two typical hospitals in Shanghai from 2013 to 2014 were consecutively collected. Personal information of psychiatrists who made admission assessment was collected separately. Results: Among the 3,529 cases, 1,890 (53.6%) were admitted because of actual harmful behaviors to self or others, while 1,639 (46.4%) were admitted with some kinds of risk, but 265 (7.5%) were admitted without any records on risk assessment checklists. Patients who were unemployed, of younger age, single status, diagnosed with schizophrenia were more likely to be admitted without any records on the checklist. Male gender, older age, and lower professional title are influencing factors that psychiatrists made no risk assessment records. Conclusions: The vast majority (92.5%) of risk assessment in IA patients were qualified in our study. In order to protect the legal rights of patients better, operational and reasonable procedures of risk assessment should be developed, such include more detailed rules to IA, systematic training of psychiatrists on IA assessment, mechanism improving doctor-patient relationship, and alternative mental health services for patients and so on.

Renal tubular cell (RTC) death and inflammation contribute to the progression of obstructive nephropathy, but its underlying mechanisms have not been fully elucidated. Here, we showed that Gasdermin E (GSDME) expression level and GSDME-N domain generation determined the RTC fate response to TNFα under the condition of oxygen-glucose-serum deprivation. Deletion of Caspase-3 (Casp3) or Gsdme alleviated renal tubule damage and inflammation and finally prevented the development of hydronephrosis and kidney fibrosis after ureteral obstruction. Using bone marrow transplantation and cell type-specific Casp3 knockout mice, we demonstrated that Casp3/GSDME-mediated pyroptosis in renal parenchymal cells, but not in hematopoietic cells, played predominant roles in this process. We further showed that HMGB1 released from pyroptotic RTCs amplified inflammatory responses, which critically contributed to renal fibrogenesis. Specific deletion of Hmgb1 in RTCs alleviated caspase11 and IL-1β activation in macrophages. Collectively, our results uncovered that TNFα/Casp3/GSDME-mediated pyroptosis is responsible for the initiation of ureteral obstruction-induced renal tubule injury, which subsequentially contributes to the late-stage progression of hydronephrosis, inflammation, and fibrosis. This novel mechanism will provide valuable therapeutic insights for the treatment of obstructive nephropathy.

Background: Sitosterolemia (STSL) is an extremely rare genetic disease. Xanthomas as the first symptom are frequently misinterpreted as familial hypercholesterolemia (FH) in children. Inappropriate treatment may deteriorate the condition of STSL. Objectives: To present the clinical and laboratory characteristics of xanthomatous children diagnosed with sitosterolemia in comparison with childhood FH with xanthomas. Methods: We summarized and compared the clinical characteristics of STSL and FH patients with xanthomas as the first manifestations and investigated the different indicators between the STSL and FH groups, as well as their diagnostic values for STSL. Results: Two tertiary pediatric endocrinology departments contributed ten STSL cases. Five of the STSL patients (50%) experienced mild anemia, whereas two (20%) had vascular complications. The xanthomas of the STSL group displayed morphologies comparable to those of the FH group. There were ten cases of homozygous FH (HoFH) with xanthomas as the predominant symptom of the control group who had no anemia. The serum cholesterol (Chol) levels of the STSL and FH groups were 12.57 (9.55 ~ 14.62) mmol/L and 17.45 (16.04 ~ 21.47) mmol/L, respectively (p value 0.002). The serum low-density lipoprotein cholesterol (LDL-c) levels of the STSL and FH groups were 9.26 ± 2.71 mmol/L and 14.58 ± 4.08 mmol/L, respectively (p value 0.003). Meanwhile, the mean platelet volume (MPV) levels of the STSL and FH groups were 11.00 (9.79 ~ 12.53) fl. and 8.95 (8.88 ~ 12.28) fl., respectively (p value 0.009). The anemia proportions of the STSL and FH groups were 50% and 0%, respectively (p value 0.033). The AUC values of Chol, LDL-c, MPV, hemoglobin (Hb) for the diagnosis of STSL were 0.910, 0.886, 0.869, 0.879, respectively. Chol ≤ 15.41 mmol/L, LDL-c ≤ 13.22 mmol/L, MPV ≥ 9.05 fl., or Hb≤120 g/L were the best thresholds for diagnosing STSL with childhood xanthomas. Conclusion The xanthoma morphology of STSL patients resembles that of FH patients. Xanthomas as the initial symptom of a child with Chol ≤ 15.41 mmol/L, LDL-c≤13.22 mmol/L, MPV ≥ 9.05 fl., or Hb≤120 g/L, he was most likely to have STSL.

The aim of the present study was to establish a simple and efficient method for isolation and culture of primary rat glomerular microvascular endothelial cells in vitro. The bilateral kidneys were taken from 7-10-day old Sprague-Dawley rats, and the renal cortex was separated. Glomeruli were obtained by cutting and continuously passing 200-mesh and 300-mesh sieves. After type IV collagenase digestion for 15-20 min, renal microvascular globules were collected for inoculation and culture. The cultured cells were identified by cell morphology observation and immunocytochemical staining with factor VIII related antigen. The results showed that the renal microvascular globules were irregularly spherical, without cysts, and the capillary loop structure was clear; after 3 days of primary culture, short spindle-shaped cells crawled out around the renal microvascular globules and gradually formed cell colonies, showing an "island-like shape" distribution; 4-5 days later, the cell colonies fused with each other; 6 days later, the cells covered the bottom of the dish, showing a typical monolayer, paving stone-like, mosaic arrangement. The immunocytochemical staining of factor VIII related antigen showed that the cytoplasm was lightly stained brownish red, and factor VIII related antigen-positive rate of cells was nearly 100%. The above results suggested that this study successfully established a method combining continuous screening and collagenase digestion for culture of primary rat glomerular microvascular endothelial cells in vitro. It provides an important tool cell for studying the mechanism of the occurrence and development of diabetic nephropathy.

Background. Although traditional Chinese medicine (TCM) has good efficacy in the treatment of mild cognitive impairment (MCI), especially memory improvement and safety, its substance basis and intervention mechanism are particularly complex and unknown. Therefore, based on network pharmacology and data mining, this study aims to explore the rules, active ingredients and mechanism of TCM in the treatment of MCI. Methods. By searching the GeneCard, OMIM, DisGeNET and DrugBank databases, we obtained the critical targets associated with MCI. We matched the components and herbs corresponding to the important targets in the TCMSP platform. Using Cytoscape 3.7.2 software, we constructed a target-component-herb network and conducted a network topology analysis to obtain the core components and herbs. Molecular docking was used to preliminarily analyze and predict the binding activities and main binding combinations of the core targets and components. Based on the analysis of the properties, flavor and meridian distribution of herbs, the rules of herbal therapy for MCI were summarized. Results. Twenty-eight critical targets were obtained after the screening. Using the TCMSP platform, 492 components were obtained. After standardization, we obtained 387 herbs. Based on the target-composition-herb network analysis, the core targets were ADRB2, ADRA1B, DPP4, ACHE and ADRA1D. According to the screening, the core ingredients were beta-sitosterol, quercetin, kaempferol, stigmasterol and luteolin. The core herbs were matched to Danshen, Yanhusuo, Gancao, Gouteng and Jiangxiang. It was found that the herbs were mainly warm in nature, pungent in taste and liver and lung in meridian. The molecular docking results showed that most core components exhibited strong binding activity to the target combination regardless of the in or out of network combination. Conclusion. The results of this study indicate that herbs have great potential in the treatment of MCI. This study provides a reference and basis for clinical application, experimental research and new drug development of herbal therapy for MCI.

To study the dynamic response of a pressurized thin-walled circular tube structure subjected to a near-field underwater explosion, deformation and damage tests of a pressurized cylindrical tube shell with different internal pressures and wall thicknesses with the effects of an underwater explosion from 2 g of explosives at different stand-off distances were carried out in a water tank. LS-DYNA finite element software was used to carry out relevant numerical simulations to explore the anti-explosion mechanism of a pressurized cylindrical shell structure affected by factors including the initial internal pressure, the thickness of the cylindrical shell, and the stand-off distance. The simulation inputs are high-speed photography images and the damage results of the cylindrical shell. The simulation results highlight the bubble pulsation, action process deformation, and energy change of the cylindrical shell. The results indicate that an increase in the initial pressure of the cylindrical shell can effectively improve its anti-explosion ability, while the different stand-off distances of r = 12 cm and r = 9 cm correspond to the same initial internal pressure. Increasing the initial internal pressure also causes the deflection difference of the cylindrical shell to decrease. The modeling results also indicate that an increase in the wall thickness may weaken the anti-explosion ability of the cylindrical shell, which has an initial internal pressure of Pr = 0.7 MPa. After an underwater explosion, the maximum displacement difference of a cylindrical shell with thicknesses of h = 1 mm and h = 1.5 mm is less than the maximum rebound distance difference. With this decrease in the distance, the proportion of the high-pressure cylindrical shell subjected to a shock wave increases while the proportion of bubble pulsation decreases. Specifically, the maximum proportions of bubble pulsation are 30% and 92% at the stand-off distances of 3 and 12 cm, respectively.

To evaluate whether serum follicle stimulating hormone (FSH) level during the early controlled ovarian stimulation can be used as a predictor of the ovarian response in the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles.The participants of this retrospective study were chosen from Reproductive Medicine Center, Weifang People's Hospital between January 2015 and December 2020.The participants of this study met the age of 20~43 years old, anti-Müllerian hormone (AMH) ≥ 1.2 ng/mL, antral follicle count (AFC) ≥ 5, and the data was complete and no cancellation cycle. Each participant was given GnRH agonist protocol and given a fixed dose of recombinant FSH in the first four days during the controlled ovarian stimulation (COS). According to the number of oocytes retrieved, the participants were divided into two different ovarian response groups. Serum FSH level after the fourth recombinant follicle stimulating hormone (rFSH) injection were compared during the different ovarian responders.The number of participants who met both the inclusion criteria and exclusion criteria was 235. Serum sFSH levels (mean: 11.76 ± 3.10 IU/L) in the inappropriate responders was significantly higher than serum sFSH levels (mean: 10.79 ± 2.52 IU/L) in the superior responders(p = 0.029). There was a weak correlation between serum sFSH levels and the number of oocytes retrieved (r = -0.134, p = 0.041). Serum sFSH levels had significant clinical valuable (p = 0.0346) in predicting the number of oocytes retrieved.Serum sFSH levels may be a potential marker to predict the ovarian response during the early COS in the IVF/ICSI cycles, which can guide the adjustment of the exogenous rFSH dose.

Osteoporosis is now a worldwide public health problem that seriously endangers human health, but its causes have not yet been fully clarified. Recently, increasing evidence suggested that polymorph...

The carbon nanoparticles film coating on top of vertically aligned carbon nanotubes on silicon substrate (CNPs/CNTs/silicon) has been prepared by the pyrolysis of FePC at 960 °C. The surface morphologies and structure of the prepared sample are characterized by Scanning Electron Microscope, X-ray energy dispersive spectroscopy and Raman Spectroscopy. The field electron emission (FEE) properties of the CNPs/CNTs are also measured. A low turn-on electric field of 1.3 V / μ m at a current density of 10 μ A / c m 2 , low threshold electric field of 1.8 V / μ m at a current density of 1 m A / c m 2 , a high emission density and good field emission stability are obtained. The above results make CNPs/CNTs/silicon an effective field emitter.

Background Primary adrenal insufficiency (PAI) in children is a rare condition and potentially lethal. The clinical characteristics are non-specific. It may be manifested as a chronic condition or crisis. The etiologies of PAI in children are different from the adult population. Therefore, diagnostic investigation becomes challenging. Methods A retrospective study was conducted at The First Affiliated Sun Yat Sen University Pediatric Endocrine unit between September 1989 and July 2016. Results A total of 434 patients (237 males, 197 females) were identified as having PAI. Congenital adrenal hyperplasia (CAH) was the most frequent etiology (83.4%, n = 362, male:female = 174:188), of which 351 (97.2%) were 21-hydroxylase deficiency (21-OH) CAH. Non-CAH etiology accounted for 11.3% (n = 49, male:female = 47:2), of which 46 (93.9%) were of non-autoimmune. The etiologies of the 49 cases were adrenoleukodystrophy (ALD; n = 22), X-linked adrenal hypoplasia congenital (X-AHC; n = 20), autoimmune polyglandular syndrome (APS; n = 3), triple A syndrome (n = 2), steroidogenic factor 1 (SF-1) gene mutation (n = 1) and adrenalectomy (n = 1). The etiology was not identified for 23 patients (5.3%, male:female =16:7). Clinical symptoms were in accordance with the incidence of genital ambiguity (42.6%), digestive symptoms (vomiting and diarrhea) (35.5%), failure to thrive (26.5%), gonadal-associated symptom (premature puberty, sexual infantilism and amenorrhea) (21.2%), hyperpigmentation (9.7%), adrenal crisis (AC; 4.1%), neurological symptoms (3.2%), fatigue (2.5%) and prolonged jaundice (2.1%). Through physical examination, 58.5% were found to have hyperpigmentation. Conclusions This study spanned 29 years at our institution. The etiology of PAI in children was mostly of congenital forms, which exhibits a wide spectrum of clinical characteristics. For etiological diagnosis, chromosomal karyotyping is recommended for female phenotype patients.

Tomato cultivars containing the Tm‐22 resistance gene have been widely known to resist tobacco mosaic virus (TMV) and tomato mosaic virus. Tomato brown rugose fruit virus (ToBRFV), a new emerging tobamovirus, can infect tomato plants carrying the Tm‐22 gene. However, the virulence determinant of ToBRFV that overcomes the resistance conferred by the Tm‐22 gene remains unclear. In this study, we substituted the movement protein (MP) encoding sequences between ToBRFV and TMV infectious clones and conducted infectivity assays. The results showed that MP was the virulence determinant for ToBRFV to infect Tm‐22 transgenic Nicotiana benthamiana plants and Tm‐22 ‐carrying tomato plants. A TMV MP chimera with amino acid residues 60–186 of ToBRFV MP failed to induce hypersensitive cell death in the leaves of Tm‐22 transgenic N. benthamiana plants. Chimeric TMV containing residues 60–186 of ToBRFV MP could, but chimeric ToBRFV containing 61–187 residues of TMV MP failed to infect Tm‐22 transgenic N. benthamiana plants, indicating that 60–186 residues of MP were important for ToBRFV to overcome Tm‐22 gene‐mediated resistance. Further analysis showed that six amino acid residues, H67, N125, K129, A134, I147, and I168 of ToBRFV MP, were critical in overcoming Tm‐22 ‐mediated resistance in transgenic N. benthamiana plants and tomato plants. These results increase our understanding of the mechanism by which ToBRFV overcomes Tm‐22 ‐mediated resistance., Six amino acid residues, H67, N125, K129, A134, I147, and I168, located in the central region of the movement protein are involved in tomato brown rugose fruit virus to evade Tm‐22 ‐mediated resistance.

In the search for treatment schemes of COVID-19, we start by examining the general weakness of coronaviruses and then identify approved drugs attacking that weakness. The approach, if successful, should identify drugs with a specific mechanism that is at least as effective as the best drugs proposed and are ready for clinical trials. All coronaviruses translate their non-structural proteins (∼16) in concatenation, resulting in a very large super-protein. Homo-harringtonine (HHT), which has been approved for the treatment of leukemia, blocks protein elongation very effectively. Hence, HHT can repress the replication of many coronaviruses at the nano-molar concentration. In two mouse models, HHT clears SARS-CoV-2 in 3 days, especially by nasal dripping of 40 ug per day. We also use dogs to confirm the safety of HHT delivered by nebulization. The nebulization scheme could be ready for large-scale applications at the onset of the next epidemics. For the current COVID-19, a clinical trial has been approved by the Ditan hospital of Beijing but could not be implemented for want of patients. The protocol is available to qualified medical facilities.

Soft machining is a key procedure in fabrication of high-strength lithium-based silicate glass ceramic (LS) restorations. This paper reports on the diamond machining-induced surface and edge chipping damage in two pre-crystalized LS materials: pre-crystallized lithium metasilicate/orthophosphate glass ceramic (Pre-LS, IPS e.max CAD) and pre-crystallized zirconia-containing lithium metasilicate glass ceramic (Pre-ZLS, Vita Suprinity). Indentation techniques were used to measure the material mechanical properties. Soft machining was conducted using a robotic controlled apparatus mimicking dental CAD/CAM machining processes at different removal rates and enabling in-process force measurement. Machined surface roughness was assessed using 3D confocal optical profilometry in terms of the average and maximum surface heights. Scanning electron microscopy was used to assess diamond tool and machined surface and edge morphology. Soft machining of both materials was dominated by brittle fracture mixed with localized ductile flow. However, the higher brittleness index of Pre-ZLS than Pre-LS yielded higher degrees of machining-induced conchoidal fractures in Pre-ZLS in comparison with irregular fractures in Pre-LS. Thus, much larger surface roughness and deeper edge chipping damage were produced in Pre-ZLS than Pre-LS. Machining forces for Pre-ZLS were significantly smaller than Pre-LS, due to the lower machinability index associated with a complex relation of the mechanical properties as well as less debris adhesion for Pre-ZLS than Pre-LS. Further, increased material removal rates resulted in significantly increased machining forces, maximum surface roughness and fracture, and edge chipping damage in both Pre-ZLS and Pre-LS materials. Therefore, optimization of soft machining processes needs to be practiced to achieve accepted surface and edge quality at balanced removal rates.