Prediction value of 18F-FDG PET/CT intratumor metabolic heterogeneity parameters for recurrence after radical surgery of stage II/III colorectal cancer.

Purpose: We explored the predictive effect of intratumor metabolic heterogeneity indices extracted from 18F-FDG PET/CT on recurrence in stage II/III colorectal cancer after radical surgery. Methods: A total of 140 stage II/III colorectal cancer patients who received preoperative 18F-FDG PET/CT and radical resection were enrolled. 18F-FDG traditional parameters including the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) under different thresholds; heterogeneity indices including the coefficient of variation with SUV 2.5 as a threshold (CV2.5), CV40%, heterogeneity index-1 (HI-1) calculated by the fixed-threshold method, and HI-2 calculated by the percentage threshold method; and clinicopathological information were collected. We concluded that relationships exist between these data and patients' disease-free survival (DFS). Results: Regional lymph node status (P < 0.001), nerve invasion (P = 0.036), tumor thrombus (P = 0.005), and HI-1 (P = 0.010) exhibited significant differences between the relapse and non-relapse groups, while SUVmax, MTV2.5, MTV40%, TLG2.5, TLG40%, CV2.5, CV40%, HI-2, and other clinicopathological factors had no differences between the relapse and non-relapse groups. Multivariate analysis demonstrated that HI-1 (HR = 1.02, 1.00-1.04, P = 0.038), regional lymph node metastasis (HR = 2.95, 1.37-6.38, P = 0.006), and tumor thrombus status (HR = 2.37, 1.13-4.99, P = 0.022) were independent factors significantly related to DFS. Conclusion: HI-1, tumor thrombus status, and regional lymph node status could predict the recurrence of stage II/III colorectal cancer after radical resection and had an advantage over other 18F-FDG PET/CT conventional parameters and heterogeneity indices.

Double-Stranded RNA-Degrading Enzymes Reduce the Efficiency of RNA Interference in Plutella xylostella.

DsRNA-degrading enzymes (dsRNases) have been recognized as important factors in reducing RNA interference (RNAi) efficiency in different insect species. However, dsRNases in Plutella xylostella are still unknown. We identified the full-length cDNAs of PxdsRNase1, PxdsRNase2, PxdsRNase3, and PxdsRNase4. Gene expression profile showed that PxdsRNase1 was mainly expressed in the hemolymph; and that PxdsRNase2 and PxdsRNase3 were mainly expressed in the intestinal tract. The expression of PxCht (Chitinase of P. xylostella) in P. xylostella larvae injected with the mixture of dsPxCht (dsRNA of PxCht) and dsPxdsRNase1 (dsRNA of PxdsRNase1), dsPxdsRNase2 (dsRNA of PxdsRNase2), or dsPxdsRNase3 (dsRNA of PxdsRNase3) was significantly higher than that in the larvae injected with the mixture of dsGFP (dsRNA of green fluorescent protein gene, GFP) and dsPxCht; the transcription level of PxCht in the larvae feeding on the mixture of dsPxCht and dsPxdsRNase1, dsPxdsRNase2, or dsPxdsRNase3 was significantly higher than that in the larvae feeding on the mixture of dsPxCht and dsGFP. The recombinant protein of PxdsRNase1 degraded dsRNA rapidly, PxdsRNase3 cleaved dsRNA without complete degradation, and PxdsRNase2 could not degrade dsRNA in vitro. These results suggested that PxdsRNases1, PxdsRNases2, and PxdsRNases3 were involved in the dsRNA degradation to reduce RNAi efficiency with different mechanisms.

Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor

Severe respiratory disease coronavirus-2 (SARS-CoV-2) causes the most devastating disease, COVID-19, of the recent century. One of the unsolved scientific questions around SARS-CoV-2 is the animal origin of this virus. Bats and pangolins are recognized as the most probable reservoir hosts that harbor the highly similar SARS-CoV-2 related viruses (SARSr-CoV-2). Here, we report the identification of a novel lineage of SARSr-CoVs, including RaTG15 and seven other viruses, from bats at the same location where we found RaTG13 in 2015. Although RaTG15 and the related viruses share 97.2% amino acid sequence identities to SARS-CoV-2 in the conserved ORF1b region, but only show less than 77.6% to all known SARSr-CoVs in genome level, thus forms a distinct lineage in the Sarbecovirus phylogenetic tree. We then found that RaTG15 receptor binding domain (RBD) can bind to and use Rhinolophus affinis bat ACE2 (RaACE2) but not human ACE2 as entry receptor, although which contains a short deletion and has different key residues responsible for ACE2 binding. In addition, we show that none of the known viruses in bat SARSr-CoV-2 lineage or the novel lineage discovered so far use human ACE2 efficiently compared to SARSr-CoV-2 from pangolin or some of the SARSr-CoV-1 lineage viruses. Collectively, we suggest more systematic and longitudinal work in bats to prevent future spillover events caused by SARSr-CoVs or to better understand the origin of SARS-CoV-2.

The Combination of Bacillus Thuringiensis and Its Engineered Strain Expressing dsRNA Increases the Toxicity against Plutella Xylostella.

RNA interference (RNAi) has been developed and used as an emerging strategy for pest management. Here, an entomopathogen Bacillus thuringiensis (Bt) was used to express the dsRNA for the control of Plutella xylostella. A vector containing a 325-bp fragment of the conserved region of P. xylostella arginine kinase gene (PxAK) flanking in two ends with the promoter Pro3α was developed and transferred into Bt 8010 and BMB171, and consequently engineered Bt strains 8010AKi and BMB171AKi expressing dsRNA of PxAK were developed. The two engineered Bt strains were separately mixed with Bt 8010 in a series of ratios, and then fed to the P. xylostella larvae. We found that 8010:8010AKi of 9:1 and 8010:BMB171AKi of 7:3 caused a higher mortality than Bt 8010. PxAK expression levels in the individuals treated with the mixtures, 8010AKi and BMB171Aki, were lower than that in the control. The intrinsic rate of increase (r) and net reproductive rate (R0) of the population treated with 8010:8010AKi of 9:1 were lower than those of the population treated with Bt 8010 or 8010AKi. We developed a Bt-mediated insect RNAi for the control of P. xylostella and demonstrated a practical approach to integrating the entomopathogen with RNAi technique for the pest management.

Origin and cross-species transmission of bat coronaviruses in China

Bats are presumed reservoirs of diverse coronaviruses (CoVs) including progenitors of Severe Acute Respiratory Syndrome (SARS)-CoV and SARS-CoV-2, the causative agent of COVID-19. However, the evolution and diversification of these coronaviruses remains poorly understood. We used a Bayesian statistical framework and sequence data from all known bat-CoVs (including 630 novel CoV sequences) to study their macroevolution, cross-species transmission, and dispersal in China. We find that host-switching was more frequent and across more distantly related host taxa in alpha-than beta-CoVs, and more highly constrained by phylogenetic distance for beta-CoVs. We show that inter-family and -genus switching is most common in Rhinolophidae and the genus Rhinolophus. Our analyses identify the host taxa and geographic regions that define hotspots of CoV evolutionary diversity in China that could help target bat-CoV discovery for proactive zoonotic disease surveillance. Finally, we present a phylogenetic analysis suggesting a likely origin for SARS-CoV-2 in Rhinolophus spp. bats.

Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial

AimsStudies have indicated that chloroquine (CQ) shows antagonism against COVID-19 in vitro. However, evidence regarding its effects in patients is limited. This study aims to evaluate the efficacy of hydroxychloroquine (HCQ) in the treatment of patients with COVID-19. Main methodsFrom February 4 to February 28, 2020, 62 patients suffering from COVID-19 were diagnosed and admitted to Renmin Hospital of Wuhan University. All participants were randomized in a parallel-group trial, 31 patients were assigned to receive an additional 5-day HCQ (400 mg/d) treatment, Time to clinical recovery (TTCR), clinical characteristics, and radiological results were assessed at baseline and 5 days after treatment to evaluate the effect of HCQ. Key findingsFor the 62 COVID-19 patients, 46.8% (29 of 62) were male and 53.2% (33 of 62) were female, the mean age was 44.7 (15.3) years. No difference in the age and sex distribution between the control group and the HCQ group. But for TTCR, the body temperature recovery time and the cough remission time were significantly shortened in the HCQ treatment group. Besides, a larger proportion of patients with improved pneumonia in the HCQ treatment group (80.6%, 25 of 31) compared with the control group (54.8%, 17 of 31). Notably, all 4 patients progressed to severe illness that occurred in the control group. However, there were 2 patients with mild adverse reactions in the HCQ treatment group. Significance: Among patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia. SignificanceAmong patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia. Trial registrationURL: https://www.clinicaltrials.gov/. The unique identifier: ChiCTR2000029559.

Nanopore target sequencing for accurate and comprehensive detection of SARS-CoV-2 and other respiratory viruses

The ongoing novel coronavirus pneumonia COVID-19 outbreak in Wuhan, China, has engendered numerous cases of infection and death. COVID-19 diagnosis relies upon nucleic acid detection; however, current recommended methods exhibit high false-negative rates, low sensitivity, and cannot identify other respiratory virus infections, thereby resulting patient misdiagnosis and impeding epidemic containment. Combining the advantages of target amplification and long-read, real-time nanopore sequencing, we developed nanopore target sequencing (NTS) to detect SARS- CoV-2 and other respiratory viruses simultaneously within 6-10 h. Parallel testing with approved qPCR kits of SARS-CoV-2 and NTS using 61 nucleic acid samples from suspected COVID-19 cases confirmed that NTS identified more infected patients as positive, and could also monitor for mutated nucleic acid sequence or other respiratory virus infection in the test sample. NTS is thus suitable for contemporary COVID-19 diagnosis; moreover, this platform can be further extended for diagnosing other viruses or pathogens.

Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin

Since the SARS outbreak 18 years ago, a large number of severe acute respiratory syndrome related coronaviruses (SARSr-CoV) have been discovered in their natural reservoir host, bats1-4. Previous studies indicated that some of those bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a novel coronavirus (nCoV-2019) which caused an epidemic of acute respiratory syndrome in humans, in Wuhan, China. The epidemic, started from December 12th, 2019, has caused 198 laboratory confirmed infections with three fatal cases by January 20th, 2020. Full-length genome sequences were obtained from five patients at the early stage of the outbreak. They are almost identical to each other and share 79.5% sequence identify to SARS-CoV. Furthermore, it was found that nCoV-2019 is 96% identical at the whole genome level to a bat coronavirus. The pairwise protein sequence analysis of seven conserved non-structural proteins show that this virus belongs to the species of SARSr-CoV. The nCoV-2019 virus was then isolated from the bronchoalveolar lavage fluid of a critically ill patient, which can be neutralized by sera from several patients. Importantly, we have confirmed that this novel CoV uses the same cell entry receptor, ACE2, as SARS-CoV.

Effect of 2.8mm clear corneal incisions in phacoemulsification on surgically induced corneal higher-order aberrations / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To compare the changes of surgically induced corneal higher order aberrations after phacoemulsification with 2.8mm clear corneal incisions at different sites.METHODS:The clinical data of 100 cases (100 eyes) of patients with cataract treated by phacoemulsification with 2.8mm clear corneal incision in our hospital from March 2015 to April 2016 were analyzed retrospectively.According to the site of incision,they were divided into Group A (temporal clear corneal incision,n =55) and Group B (upper clear corneal incision,n=45).Changes of the best corrected visual acuity (BCVA),surgically induced astigmatism (SIA) and corneal topography were compared between the two groups before surgery,at 1d,1wk,1 and 3mo after surgery.The corneal wavefront aberrations were measured by wavefront aberration analyzer,and the changes of higher-order aberrations in corneal 6mm range were recorded.RESULTS:The BCVA of two groups decreased at 1d,1wk,1 and 3mo after surgery (P＜0.05),and the BCVA of Group A at 1d,1wk,and 1mo after surgery was lower than that of Group B (P＜0.05).SIA of the two groups decreased at 1wk,1 and 3mo after surgery (P＜0.05),and the SIA of Group A at different time points after surgery were lower than those of Group B (P＜0.05).The surface asymmetry index (SAI) and the surface rule index (SRI) of the two groups increased at 1 d after surgery,and were gradually decreased at 1wk,1 and 3mo after surgery.The SRI and SAI in Group A were lower than those in Group B at 1d and 1wk after surgery (P＜ 0.05).The total corneal higher-order aberrations (tHOAs) and four-order spherical aberration (SA)showed significant differences between the two groups at 3mo after surgery (P＜0.05).CONCLUSION:The application of 2.8mm temporal clear corneal incision in phacoemulsification can promote the recovery of visual acuity,reduce the effect of surgery on corneal shape,and reduce corneal higher-order aberrations.

Strategy and effect of Oncomelania hupensis snail control in inside-embank-ment areas in Junshan District ,Hunan Province from 1998 to 2017 / 中国血吸虫病防治杂志

Objective To explore the strategy and countermeasures of Oncomelania hupensis snail control and evaluate the effect in inside-embankment areas of lake-type schistosomiasis endemic area,for providing the effective method for controlling and interrupting the schistosomiasis transmission. Methods The data of schistosomiasis epidemic and its control and preven-tion were collected in Junshan District,Hunan Province,and the effect of snail control countermeasures were evaluated and the trend of indexes of snails was drafted in the inside-embankment areas of Junshan District,Hunan Province from 1998 to 2007. Results The area with snails in the inside embankment areas of Junshan District decreased by 98.43%,from 1496.66 hm2 in 1998 to 23.48 hm2 in 2017. The occurrence rate and average density of of living snails decreased from 20.61%and 0.45 snail/0.1 m2 in 2003 to 2.06%and 0.03 snail/0.1 m2 in 2017. The highest area with schistosome infected snails was found in 2001 and the total area was 79.36 hm2,however,no infected snails were found since 2007. The total fiscal investment for schistosomiasis pre-vention and control was 398.857 million RMB in Junshan District,including molluscicide(81.7709 million RMB)and environ-ment reform(213.5 million RMB)respectively. Conclusion The comprehensive measures,mainly including the combination of molluscicide and environment reform have gotten a significant effect in snail control and elimination in the inside-embankment areas,but the snail surveillance still need to be strengthened in the historic areas with snails.

Highly diastereroselective synthesis of dihydrofurans and dihydropyrroles via pyridine catalyzed formal [4+1] annulation.

A pyridine-catalyzed ylide cyclization affording dihydrofurans and dihydropyrroles has been developed. In the presence of a catalytic amount of pyridine and Fe(Tcpp)Cl, α-ylidene-ß-diketones and α,ß-unsaturated imines react with diazoacetates providing dihydrofurans and dihydropyrroles respectively, in up to 96% yield with high diastereoselectivities.

Highly selective ylide-initiated Michael addition/cyclization reaction for synthesis of cyclohexadiene epoxide and vinylcyclopropane derivatives.

On the basis of the reactions of camphor-derived sulfur ylide with alpha,beta-unsaturated ketone, highly efficient and selective synthesis of optically active cyclohexadiene epoxides and vinylcyclopropanes with excellent diastereoselectivities, moderate to high enantioselectivities, and yields has been achieved.

One-pot highly diastereoselective synthesis of cis-vinylaziridines via the sulfur ylide-mediated aziridination and palladium(0)-catalyzed isomerization.

Highly diastereoselective synthesis of cis-trisubstituted vinylaziridines containing a quaternary carbon center is realized by a one-pot protocol in which the combination of sulfur ylide-mediated aziridination of cyclic ketimines and Pd(0)-catalyzed isomerization is employed successfully.

Multistep one-pot Wittig/Nazarov reaction for construction of cyclopentenone with diazo compounds and acid chlorides.

A facile multistep one-pot synthesis of single or fused cyclopentenones has been developed. The sequence involves a transition metal-catalyzed ylide formation/Wittig Olefination/Nazarov Cyclization.

Tandem Michael addition/ylide epoxidation for the synthesis of highly functionalized cyclohexadiene epoxide derivatives.

A highly efficient diastereoselective synthesis of cyclohexadiene epoxide derivatives with a multi-stereocenter has been developed via a tandem ylide Michael addition/epoxidation. By employing a chiral sulfonium ylide, up to 96% ee can be achieved in good yields.