Sequence Analysis of TNFRSF13b, Encoding TACI, in a Patient with Very Early Onset Inflammatory Bowel Disease: a Case Report

Very early onset inflammatory bowel disease (VEO-IBD), IBD diagnosed before 6 years of age, frequently presents with increased severity, aggressive progression, and often poor response to conventional treatments. Although the cause of IBD is generally considered to be intestinal immune dysfunction induced by polygenic mutations and environment and other factors, VEO-IBD has a stronger genetic susceptibility specifically the neonatal- or infantile-onset IBD. Herein we report compound heterozygous mutations in the tumor necrosis factor receptor superfamily member 13b (TNFRSF13B) gene in a 3-year-old male that was admitted to our hospital with lasted jaundice, repeated fever and diarrhea in May 2014 at 2-month-old. He was diagnosed with VEO-IBD based on clinical, laboratory and histopathological examination. However, he was unresponsive to the conventional therapy, including the nutritional support therapy, antibiotic and immunosuppressive treatment, and surgical release of neonatal intestinal obstruction. Novel compound heterozygous mutations, c.[365G>A];[452C>T](p.[R122Q];[P151L]), were discovered in TNFRSF13B, encoding TACI, for this patient.

Solar-blind avalanche photodetector based on epitaxial Ga_(2)O_(3)/La_(0.8)Ca_(0.2)MnO_(3) pn heterojunction with ultrahigh gain

Ga_(2)O_(3)-based avalanche photodetectors(APDs) have gained increasing attention because of their excellent photoelectric conversion capability in the UV solar-blind region. Integrating high-quality epitaxial Ga_(2)O_(3) with p-type semiconductor remains an open challenge associated with the integration difficulty on alleviating its defects and dislocations. Herein,we construct an APD consisting of epitaxial β-Ga_(2)O_(3)/La_(0.8)Ca_(0.2)MnO_(3) heterostructure. The pn junction APDs exhibit a high responsivity of 568 A/W as well as an enhanced avalanche gain of up to 3.0 × 10~5 at a reverse bias voltage of 37.9 V. The integration capability demonstrated in this work provides exciting opportunities for further development of high-performance Ga_(2)O_(3)-based electronics and optoelectronics.

Trends in cancer mortality in China from 2004 to 2018:A nationwide longitudinal study

Background:The long-term trend in cancer death in a rapidly developing country provides information for cancer prophylaxis.Here,we aimed to identify the trends in cancer mortality in China during the 2004-2018 period.Methods:Using raw data from the national mortality surveillance system of China,we assessed the mortalities of all cancer and site-specific cancers during the 2004-2018 period.The participants were divided into three age groups:≥65 years,40-64 years,and≤39 years.Changing trends in cancer death by gender,residency,and tumor location were estimated using fitting joinpoint models to log-transformed crude mortality rates(CMRs)and age-standardizedmortality rates(ASMRs).Results:Cancer death accounted for 24% of all-cause of death in China during 2014-2018.The CMR of all cancer was 150.0 per 100,000 persons.Cancer was the leading cause of death in the population<65 years.The six major cancer types(lung/bronchus cancer,liver cancer,stomach cancer,esophagus cancer,colorectal cancer,and pancreas cancer)accounted for 75.85% of all cancer deaths.The CMR of all cancer increased while the ASMR decreased during 2014-2018(P<0.001).Lung/bronchus cancer and liver cancer were the leading causes of cancer death in the population<65 years,accounting for 45.31%(CMR)and 44.35%(ASMR)of all cancer death,respectively.The ASMR of liver cancer was higher in the 40-64 years population than in the≥65 years population,in contrast to the other five major cancers.The ASMRs of liver cancer,stomach cancer,and esophagus cancer decreased although they were higher in rural residents than in urban residents;the ASMRs of lung/bronchus cancer,colorectal cancer,and pancreas cancer increased in rural residents although they were higher in urban residents than in rural residents during 2014-2018.Conclusion:Although the ASMR of all cancer decreased in China during 2004-2018,lung/bronchus cancer and liver cancer remained the leading causes of cancer-related premature death.Lung/bronchus cancer,colorectal cancer,and pancreas cancer increased in rural residents.

Characterization of SARS-CoV-2 worldwide transmission based on evolutionary dynamics and specific viral mutations in the spike protein

Background:The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome-related coronavirus-2(SARS-CoV-2)is pandemic.However,the origins and global transmission pattern of SARS-CoV-2 remain largely unknown.We aimed to characterize the origination and transmission of SARS-CoV-2 based on evolutionary dynamics.Methods:Using the full-length sequences of SARS-CoV-2 with intact geographic,demographic,and temporal information worldwide from the GISAID database during 26 December 2019 and 30 November 2020,we constructed the transmission tree to depict the evolutionary process by the R package"outbreaker".The affinity of the mutated receptor-binding region of the spike protein to angiotensin-converting enzyme 2(ACE2)was predicted using mCSM-PPI2 software.Viral infectivity and antigenicity were tested in ACE2-transfected HEK293T cells by pseudovirus transfection and neutralizing antibody test.Results:From 26 December 2019 to 8 March 2020,early stage of the COVID-19 pandemic,SARS-CoV-2 strains identified worldwide were mainly composed of three clusters:the Europe-based cluster including two USA-based subclusters;the Asia-based cluster including isolates in China,Japan,the USA,Singapore,Australia,Malaysia,and Italy;and the USA-based cluster.The SARS-CoV-2 strains identified in the USA formed four independent clades while those identified in China formed one clade.After 8 March 2020,the clusters of SARS-CoV-2 strains tended to be independent and became"pure"in each of the major countries.Twenty-two of 60 mutations in the receptor-binding domain of the spike protein were predicted to increase the binding affinity of SARS-CoV-2 to ACE2.Of all predicted mutants,the number of E484K was the largest one with 86585 sequences,followed by S477N with 55442 sequences worldwide.In more than ten countries,the frequencies of the isolates with E484K and S477N increased significantly.V367F and N354D mutations increased the infectivity of SARS-CoV-2 pseudoviruses(P<0.001).SARS-CoV-2 with V367F was more sensitive to the S1-targeting neutralizing antibody than the wild-type counterpart(P<0.001).Conclusions:SARS-CoV-2 strains might have originated in several countries simultaneously under certain evolutionary pressure.Travel restrictions might cause location-specific SARS-CoV-2 clustering.The SARS-CoV-2 evolution appears to facilitate its transmission via altering the affinity to ACE2 or immune evasion.