ZFYVE19 deficiency: a ciliopathy involving failure of cell division, with cell death.

BACKGROUND AND AIMS: Variants in ZFYVE19 underlie a disorder characterised by progressive portal fibrosis, portal hypertension and eventual liver decompensation. We aim to create an animal model to elucidate the pathogenic mechanism. METHODS: Zfyve19 knockout (Zfyve19-/- ) mice were generated and exposed to different liver toxins. Their livers were characterised at the tissue, cellular and molecular levels. Findings were compared with those in wild-type mice and in ZFYVE19-deficient patients. ZFYVE19 knockout and knockdown retinal pigment epithelial-1 cells and mouse embryonic fibroblasts were generated to study cell division and cell death. RESULTS: The Zfyve19-/- mice were normal overall, particularly with respect to hepatobiliary features. However, when challenged with α-naphthyl isothiocyanate, Zfyve19-/- mice developed changes resembling those in ZFYVE19-deficient patients, including elevated serum liver injury markers, increased numbers of bile duct profiles with abnormal cholangiocyte polarity and biliary fibrosis. Failure of cell division, centriole and cilia abnormalities, and increased cell death were observed in knockdown/knockout cells. Increased cell death and altered mRNA expression of cell death-related signalling pathways was demonstrated in livers from Zfyve19-/- mice and patients. Transforming growth factor-ß (TGF-ß) and Janus kinase-Signal Transducer and Activator of Transcription 3 (JAK-STAT3) signalling pathways were upregulated in vivo, as were chemokines such as C-X-C motif ligands 1, 10 and 12. CONCLUSIONS: Our findings demonstrated that ZFYVE19 deficiency is a ciliopathy with novel histological features. Failure of cell division with ciliary abnormalities and cell death activates macrophages and may thus lead to biliary fibrosis via TGF-ß pathway in the disease.

The innovative checkpoint inhibitors of lung adenocarcinoma, cg09897064 methylation and ZBP1 expression reduction, have implications for macrophage polarization and tumor growth in lung cancer.

Lung cancer, a prevalent and aggressive disease, is characterized by recurrence and drug resistance. It is essential to comprehend the fundamental processes and discover novel therapeutic objectives for augmenting treatment results. Based on our research findings, we have identified a correlation between methylation of cg09897064 and decreased expression of ZBP1, indicating a link to unfavorable prognosis in patients with lung cancer. Furthermore, these factors play a role in macrophage polarization, with ZBP1 upregulated in M1 macrophages compared to both M0 and M2 polarized macrophages. We observed cg09897064 methylation in M2 polarization, but not in M0 and M1 polarized macrophages. ATACseq analysis revealed closed chromatin accessibility of ZBP1 in M0 polarized macrophages, while open accessibility was observed in both M1 and M2 polarized macrophages. Our findings suggest that ZBP1 is downregulated in M0 polarized macrophages due to closed chromatin accessibility and downregulated in M2 polarized macrophages due to cg09897064 methylation. Further investigations manipulating cg09897064 methylation and ZBP1 expression through overexpression plasmids and shRNAs provided evidence for their role in modulating macrophage polarization and tumor growth. ZBP1 inhibits M2 polarization and suppresses tumor growth, while cg09897064 methylation promotes M2 polarization and macrophage-induced tumor growth. In mechanism investigations, we found that cg09897064 methylation impairs CEBPA binding to the ZBP1 promoter, leading to decreased ZBP1 expression. Clinical experiments were conducted to validate the correlation between methylation at cg09897064, ZBP1 expression, and macrophage M2 polarization. Targeting these factors may hold promise as a strategy for developing innovative checkpoint inhibitors in lung cancer treatment.

Latent class analysis of healthcare workers' perceptions of workers' job demands in mobile cabin hospitals in China.

BACKGROUND: Owing to the outbreak of the Omicron variant of SARS-CoV-2 in Shanghai, China, partitioned dynamic closure and control management plans were implemented on March 28, 2022. This created huge emergency pressure on Shanghai's medical and healthcare systems. However, the perceptions of job demands of healthcare workers (HCWs) and classification of frontline HCWs in mobile cabin hospitals are unknown. METHODS: In this study, we investigated the job demands of 1223 frontline HCWs working in mobile cabin hospitals during the COVID-19 pandemic April 2022 to May 2022. We performed latent class analysis to identify classification features of job demands. A binary multivariate logistic regression model was used to explore the influencing factors of latent class. RESULTS: The total mean job demand score was 132.26 (SD = 9.53), indicating a high level of job demand. A two-class model provided the best fit. The two classes were titled "middle-demand group" (17.66%) and "high-demand group" (82.34%). A regression analysis suggested that female HCWs, HCWs satisfied with the doctor/nurse-patient relationship, HCWs who believed that the risk of working in mobile cabin hospitals was high, and HCWs without physical discomfort during the pandemic were more likely to be in the "high-demand group". CONCLUSION: Characteristics of the "high-demand group" subtype suggest that attention should be paid to the physical condition of frontline HCWs and the job demands of female HCWs. Managers should strengthen the training of HCWs in terms of their communication skills as well as their knowledge and technical skills to aid epidemic prevention and control.

Cross-sectional survey of smartphone addiction and its relationship with personality traits among medical students.

OBJECTIVE: To understand the current smart phone addiction tendency (SPAT) in medical university students and relationship with personality traits. METHODS: A cross-sectional study from September 2019 to December 2019 selected medical students from Hubei University of China by cluster sampling. Questionnaires were administered to measure smart phone addiction tendency and personality traits. RESULTS: The prevalence of SPAT among 972 medical students was 24.3%. The prevalence was higher in students from one-child family than those with siblings (28.2% vs. 21.7%), and higher among students from urban families than those from rural ones (29.2% vs. 19.7%).Multivariate logistic regression analysis showed that extraversion and neuroticism were correlated with SPAT, with odds ratio and 95% confidence interval being equal to 1.070 (1.011-1.133) and 0.838 (0.795-0.844), respectively. CONCLUSIONS: The prevalence of SPAT was high in medical college students. Extraversion and neuroticism were risk and protective factors for SPAT. Long duration phone use and a low number of physical workouts predicted high SPAT.

Ag@Pyc Nanocapsules as Electrochemiluminescence Emitters for an Ultrasensitive Assay of the APE1 Activity.

Herein, Ag@pyrenecarboxaldehyde nanocapsules (Ag@Pyc nanocapsules) as emitters were prepared to construct an ultrasensitive electrochemiluminescence (ECL) biosensor for the detection of the human apurinic/apyrimidinic endonuclease1 (APE1) activity. Ag nanoparticles on the surface of Pyc nanocapsules as coreaction accelerators could significantly promote coreactant peroxydisulfate (S2O82-) to generate massive reactive intermediates of sulfate radical anion (SO4•-), which interacted with the Pyc nanocapsules to achieve a strong ECL response. In addition, with the aid of APE1-triggered 3D DNA machine, trace target could be converted into a large number of mimic targets (MTs), which were positively correlated with the activity of APE1. Consequently, the proposed ECL biosensor realized an ultrasensitive detection of APE1 activity with an exceptional linear working range from 5 × 10-10 to 5 × 10-4 U·µL-1 and a lower limit of detection of 1.36 × 10-11 U·µL-1. This strategy provided a new approach to construct an efficient ternary system for the detection of biomolecules and early diagnosis of diseases.

Identification of sitagliptin binding proteins by affinity purification mass spectrometry.

Type 2 diabetes mellitus (T2DM) is recognized as a serious public health concern with increasing incidence. The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin has been used for the treatment of T2DM worldwide. Although sitagliptin has excellent therapeutic outcome, adverse effects are observed. In addition, previous studies have suggested that sitagliptin may have pleiotropic effects other than treating T2DM. These pieces of evidence point to the importance of further investigation of the molecular mechanisms of sitagliptin, starting from the identification of sitagliptin-binding proteins. In this study, by combining affinity purification mass spectrometry (AP-MS) and stable isotope labeling by amino acids in cell culture (SILAC), we discover seven high-confidence targets that can interact with sitagliptin. Surface plasmon resonance (SPR) assay confirms the binding of sitagliptin to three proteins, i. e., LYPLAL1, TCP1, and CCAR2, with binding affinities (K D) ranging from 50.1 µM to 1490 µM. Molecular docking followed by molecular dynamic (MD) simulation reveals hydrogen binding between sitagliptin and the catalytic triad of LYPLAL1, and also between sitagliptin and the P-loop of ATP-binding pocket of TCP1. Molecular mechanics Poisson-Boltzmann Surface Area (MMPBSA) analysis indicates that sitagliptin can stably bind to LYPLAL1 and TCP1 in active sites, which may have an impact on the functions of these proteins. SPR analysis validates the binding affinity of sitagliptin to TCP1 mutant D88A is ~10 times lower than that to the wild-type TCP1. Our findings provide insights into the sitagliptin-targets interplay and demonstrate the potential of sitagliptin in regulating gluconeogenesis and in anti-tumor drug development.

Comparison of nitrogen losses from different manure treatment and application management systems in China.

There is a worldwide focus on reducing the environmental impacts of livestock manure management. In China, there are different manure treatment and application modes, including complete treatment to remove nitrogen (N) for direct discharge into watercourses. But we lack a systematic quantitative comparison of the environmental losses that occur from different management modes. We used an example farm of 10,000 finisher pigs to quantitatively analyze the annual N losses from land application (LA) and treatment to remove N from manure to the level of discharge consent (DS) under 24 sub-modes. This is an important study to unravel the effect of choice of different manure management systems on subsequent N losses. The results showed that the N losses from the LA mode (52.6% of total N excretion) were significantly lower than that from the DS mode (75.9%). Compared with other sub-modes, N emission from whole slurry injection was the smallest, accounting for 43.2% of total N excretion. NH3-N was the main source of N loss which accounted for 72.9% and 50.2% in LA and DS mode, respectively. The lowest N emission of LA mode with mitigation options, including slurry store covers, composting with bio-filter deodorization and injection application, was 28.8% of total N excretion, which is only 42.2% of N emission from DS mode with mitigation options. Insights from this systematic study of different manure management modes in China show the imperative of control ammonia emission for China, and provide guidance to the sustainable manure management in rapidly developing countries.

[Application of ultrasound-guided endoscopic retrograde appendicitis therapy in children with appendix-related chronic abdominal pain]. / è¶ å£°å¼•å¯¼å† é•œä¸‹é€†è¡Œé˜‘å°¾ç‚Žæ²»ç–—æœ¯åœ¨é˜‘å°¾ç›¸å ³æ ¢æ€§è ¹ç—›æ‚£å„¿ä¸­çš„åº”ç”¨ä»·å€¼.

OBJECTIVES: To study the clinical efficacy of ultrasound-guided endoscopic retrograde appendicitis therapy in children with appendix-related chronic abdominal pain. METHODS: A retrospective analysis was performed on the medical data of 30 children with the chief complaint of chronic abdominal pain who were admitted from August 2019 to May 2021. All the children were found to have inflammation of the appendix or intracavitary stool and fecalith by ultrasound and underwent ultrasound-guided endoscopic retrograde appendicitis therapy. The medical data for analysis included clinical manifestations, endoscopic findings, white blood cell count, neutrophil percentage, length of hospital stay, and cure rate. RESULTS: Among the 30 children with chronic abdominal pain, there were 13 boys (43%) and 17 girls (57%), with a mean age of (9±3) years (range 3-15 years) at diagnosis. The median duration of the disease was 12 months, and the median length of hospital stay was 3 days. The children had a median white blood cell count of 6.7×109/L and a neutrophil percentage of 50%±13%. Fecalith and a large amount of feces were flushed out of the appendix cavity for 21 children (70%) during surgery. The follow-up rate was 97% (29/30), and the median follow-up time was 11 months (range 5-26 months). Of the 29 children, abdominal pain completely disappeared in 27 children (93%). CONCLUSIONS: Ultrasound-guided endoscopic retrograde appendicitis therapy is effective in children with chronic abdominal pain caused by feces or fecalith in the appendix cavity.

Nsp2 has the potential to be a drug target revealed by global identification of SARS-CoV-2 Nsp2-interacting proteins.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health threat since December 2019, and there is still no highly effective drug to control the pandemic. To facilitate drug target identification for drug development, studies on molecular mechanisms, such as SARS-CoV-2 protein interactions, are urgently needed. In this study, we focused on Nsp2, a non-structural protein with largely unknown function and mechanism. The interactome of Nsp2 was revealed through the combination of affinity purification mass spectrometry (AP-MS) and stable isotope labeling by amino acids in cell culture (SILAC), and 84 proteins of high-confidence were identified. Gene ontology analysis demonstrated that Nsp2-interacting proteins are involved in several biological processes such as endosome transport and translation. Network analysis generated two clusters, including ribosome assembly and vesicular transport. Bio-layer interferometry (BLI) assay confirmed the bindings between Nsp2- and 4-interacting proteins, i.e. STAU2 (Staufen2), HNRNPLL, ATP6V1B2, and RAP1GDS1 (SmgGDS), which were randomly selected from the list of 84 proteins. Our findings provide insights into the Nsp2-host interplay and indicate that Nsp2 may play important roles in SARS-CoV-2 infection and serve as a potential drug target for anti-SARS-CoV-2 drug development.

Changes in Triterpenes in Alismatis rhizoma after Processing Based on Targeted Metabolomics Using UHPLC-QTOF-MS/MS.

Alismatis rhizoma (AR) has been used as an herbal medicine in China for over a thousand years. Crude AR, salt-processed AR (SAR), and bran-processed AR (BAR) are recorded in the Pharmacopoeia of the People's Republic of China. However, the differences of chemical composition between crude AR and its processing products remain limited. In this study, triterpenes were identified from crude AR, SAR, and BAR by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight-mass spectrometer (UHPLC-QTOF-MS/MS). Subsequently, the differences of triterpenes between the crude AR and processed ARs were compared via a targeted metabolomics approach. Finally, a total of 114 triterpenes were identified, of which 83, 100, and 103 triterpenes were found in crude AR, SAR, and BAR, respectively. After salt-processing, there were 17 triterpenes newly generated, 7 triterpenes with trends of increasing, and 37 triterpenes decreased. Meanwhile, 56 triterpenes including 21 newly generated and 35 with significant increases were observed in BAR. This study could be benefit to investigate the processing mechanism of AR, as well as support their clinical applications.

Fatty acylCoA synthetase FadD13 regulates proinflammatory cytokine secretion dependent on the NF-κB signalling pathway by binding to eEF1A1.

Mycobacterium tuberculosis (Mtb) manipulates multiple host defence pathways to survive and persist in host cells. Understanding Mtb-host cell interaction is crucial to develop an efficient means to control the disease. Here, we applied the Mtb proteome chip, through separately interacting with H37Ra and H37Rv stimulated macrophage lysates, screened 283 Mtb differential proteins. Through primary screening, we focused on fatty acylCoA synthetase FadD13. Mtb FadD13 is a potential drug target, but its role in infection remains unclear. Deletion of FadD13 in Mtb reduced the production of proinflammatory cytokines IL-1ß, IL-18, and IL-6. Bimolecular fluorescence complementation and colocalization showed that the binding partner of FadD13 in macrophage was eEF1A1 (a translation elongation factor). Knockdown eEF1A1 expression in macrophage abrogated the promotion of proinflammatory cytokines induced by FadD13. In addition, ΔfadD13 mutant decreased the expression of the NF-κB signalling pathway related proteins p50 and p65, so did the eEF1A1 knockdown macrophage infected with H37Rv. Meanwhile, we found that deletion of FadD13 reduced Mtb survival in macrophages during Mtb infection, and purified FadD13 proteins induced broken of macrophage membrane. Taken together, FadD13 is crucial for Mtb proliferation in macrophages, and it plays a key role in the production of proinflammatory cytokines during Mtb infection.

Supersensitive Photoelectrochemical Aptasensor Based on Br,N-Codoped TiO2 Sensitized by Quantum Dots.

Here, we fabricated a novel photoelectrochemical (PEC) aptasensor based on Br,N-codoped TiO2/CdS quantum dots (QDs) sensitization structure with excellent energy level arrangement for supersensitive detection of carcinoembryonic antigen (CEA). The prepared Br,N-codoped TiO2 could reduce the energy bandwidth of TiO2 from 3.2 to 2.88 eV, which could dramatically reduce the basic signal and obviously broaden the absorption of light (400-700 nm). In addition, the energy bandwidth of Br,N-codoped TiO2 (2.88 eV) matched well with that of CdS QDs (2.4 eV), making CdS QDs an ideal signal enhancer for amplifying the photocurrent signal of Br,N-codoped TiO2. More importantly, the constructed Br,N-codoped TiO2/CdS QDs sensitization structure with narrow energy level gradient enabled the effective promotion of electron-transfer capability and dramatic improvement of photoelectric conversion efficiency. Simultaneously, a small amount of the CEA was transformed into substantial single-chain DNA (T-DNA) via exonuclease III (Exo-III)-assisted cycle strategy. Under optimum conditions, the designed PEC aptasensor demonstrated a wide detection range from 1 fg/mL to 1 ng/mL and a low detection limit as 0.46 fg/mL for CEA assay. This strategy prepared a new photoactive material to markedly improve photoelectric conversion efficiency and initiated a new way to realize the highly sensitive PEC biomolecules detection.

Cosensitization Strategy with Cascade Energy Level Arrangement for Ultrasensitive Photoelectrochemical Protein Detection.

Here, a photoelectrochemical (PEC) biosensor was established by a cosensitization strategy with cascade energy level arrangement for ultrasensitive detection of prostate-specific antigen (PSA). The proposed cosensitization strategy was based on the well-matched energy level arrangement of four kinds of organic photoactive materials, in which poly{4,8-bis[5-(2-ethylhexyl)thiophen-2-yl]benzo[1,2- b:4,5- b']dithiophene-2,6-diyl- alt-3-fluoro-2-[(2-ethylhexyl)-carbonyl]thieno[3,4- b]thiophene-4,6-diyl} (PTB7-Th) was used as the photoactive material and perylenetetracarboxyl diimide (PDI), fullerene (nano-C60), and polyaniline (PANI) were employed as the sensitizers. The resulting PTB7-Th/PDI/nano-C60/PANI cascade cosensitization structure with narrow energy level gradient (<0.54 eV) could effectively improve electron transfer capability, obviously raise light energy utilization and significantly enhance photoelectric conversion efficiency, leading to dramatically enhanced photocurrent response. Using PSA as a target model, the proposed PEC biosensor exhibited high sensitivity and excellent stability with a wide detection range from 1 fg/mL to 0.1 ng/mL and a detection limit of 0.43 fg/mL. Moreover, the proposed PEC biosensor provides a cascade cosensitization strategy that could significantly improve PEC performances and open up a promising platform to establish high selectivity, stability, and ultrasensitive analytical techniques.

Global environmental costs of China's thirst for milk.

China has an ever-increasing thirst for milk, with a predicted 3.2-fold increase in demand by 2050 compared to the production level in 2010. What are the environmental implications of meeting this demand, and what is the preferred pathway? We addressed these questions by using a nexus approach, to examine the interdependencies of increasing milk consumption in China by 2050 and its global impacts, under different scenarios of domestic milk production and importation. Meeting China's milk demand in a business as usual scenario will increase global dairy-related (China and the leading milk exporting regions) greenhouse gas (GHG) emissions by 35% (from 565 to 764 Tg CO2eq ) and land use for dairy feed production by 32% (from 84 to 111 million ha) compared to 2010, while reactive nitrogen losses from the dairy sector will increase by 48% (from 3.6 to 5.4 Tg nitrogen). Producing all additional milk in China with current technology will greatly increase animal feed import; from 1.9 to 8.5 Tg for concentrates and from 1.0 to 6.2 Tg for forage (alfalfa). In addition, it will increase domestic dairy related GHG emissions by 2.2 times compared to 2010 levels. Importing the extra milk will transfer the environmental burden from China to milk exporting countries; current dairy exporting countries may be unable to produce all additional milk due to physical limitations or environmental preferences/legislation. For example, the farmland area for cattle-feed production in New Zealand would have to increase by more than 57% (1.3 million ha) and that in Europe by more than 39% (15 million ha), while GHG emissions and nitrogen losses would increase roughly proportionally with the increase of farmland in both regions. We propose that a more sustainable dairy future will rely on high milk demanding regions (such as China) improving their domestic milk and feed production efficiencies up to the level of leading milk producing countries. This will decrease the global dairy related GHG emissions and land use by 12% (90 Tg CO2eq reduction) and 30% (34 million ha land reduction) compared to the business as usual scenario, respectively. However, this still represents an increase in total GHG emissions of 19% whereas land use will decrease by 8% when compared with 2010 levels, respectively.

Splicing analysis of rare/novel synonymous or intronic variants identified in ABCB11 heterozygotes presenting as progressive intrahepatic cholestasis with low γ-glutamyltransferase.

AIM: The aim of this study was to analyze the pathogenicity of rare/novel synonymous or intronic variants identified in ABCB11 heterozygotes presenting as progressive intrahepatic cholestasis with low γ-glutamyltransferase. METHODS: The enrolled variants were identified in ABCB11 between October 2009 and June 2016. The effects on pre-RNA splicing were analyzed by in silico tools and minigene splicing assay. RESULTS: There were three intronic (c.908 + 5G > A, c.2815-8A > G, and c.612-15_-6del10bp) and two synonymous (c.1809G > A, p.K603 K and c.2418C > T, p.G806G) variants with unknown significance identified in ABCB11 of five ABCB11 heterozygotes. Parental studies were carried out for four patients, and revealed that the variants with unknown significance were compound heterozygous with other pathogenic variants. The five variants with unknown significance had minor allele frequency <0.1% or were absent from controls, and had positive prediction results by in silico tools. The effects on pre-RNA splicing were further confirmed by minigene splicing assay. c.908 + 5A caused abnormal splicing in at least 78.5 ± 3.8% of products using a cryptic splice site (ss) 22 nucleotides (nt) upstream of the wild-type (WT) 5'ss. Seven nucleotides of intron 22 upstream of the WT 3'ss was retained for all products from c.2815-8G. c.612-15_-6del caused exon 8 skipping in 24.8 ± 7.7% of products, and 55 nt of exon 8 downstream of the WT 3'ss removal in remaining products. c.1809A led to exon 15 skipping. c.2418 T removed exon 20 and 62 nt of exon 21 downstream of the WT 3'ss by using a cryptic ss. CONCLUSIONS: We successfully identified five pathogenic synonymous or intronic variants with some common features. These features might help to choose the right variant for further functional assay.

Novel NBAS mutations and fever-related recurrent acute liver failure in Chinese children: a retrospective study.

BACKGROUND: Underlying causes in Chinese children with recurrent acute liver failure (RALF), including liver crises less than full acute liver failure, are incompletely understood. We sought to address this by searching for genes mutated in such children. METHODS: Five unrelated Chinese boys presenting between 2012 and 2015 with RALF of unexplained etiology were studied. Results of whole exome sequencing were screened for mutations in candidate genes. Mutations were verified in patients and their family members by Sanger sequencing. All 5 boys underwent liver biopsy. RESULTS: NBAS was the only candidate gene mutated in more than one patient (biallelic mutations, 3 of 5 patients; 5 separate mutations). All NBAS mutations were novel and predictedly pathogenic (frameshift insertion mutation c.6611_6612insCA, missense mutations c.2407G > A and c.3596G > A, nonsense mutation c.586C > T, and splicing-site mutation c.5389 + 1G > T). Of these mutations, 3 lay in distal (C-terminal) regions of NBAS, a novel distribution. Unlike the 2 patients without NBAS mutations, the 3 patients with confirmed NBAS mutations all suffered from a febrile illness before each episode of liver crisis (fever-related RALF), with markedly elevated alanine aminotransferase and aspartate aminotransferase activities 24-72 h after elevation of body temperature, succeeded by severe coagulopathy and mild to moderate jaundice. CONCLUSIONS: As in other countries, so too in China; NBAS disease is a major cause of fever-related RALF in children. The mutation spectrum of NBAS in Chinese children seems different from that described in other populations.

Quantitative proteomic analysis of host responses triggered by Mycobacterium tuberculosis infection in human macrophage cells.

Macrophages are primary host of Mycobacterium tuberculosis (M.tb) and the central effector of in vivo innate immune responses against bacteria. Though the interaction between macrophages and mycobacteria has been widely investigated, the molecular mechanisms of M.tb pathogenesis in macrophages are still not clear. In this work, we investigated the altered protein expression profiles of macrophages after virulent H37Rv strain and avirulent H37Ra strain infection by tandem mass tag-based quantitative proteomics. Among 6762 identified proteins of macrophages, the expression levels of 235 proteins were significantly altered, which is supposed to be related to the infection of different strains. By bioinformatics analysis at systems level, we found that these proteins are mainly involved in the biological process of apoptosis, blood coagulation, oxidative phosphorylation, and others. The enormous variation in protein profiles between macrophages infected with H37Ra and H37Rv suggests the existence of four different immunity mechanisms that decide the fates of macrophages and M.tb. These data may provide a better understanding of M.tb pathogenesis within the host, which contributes to the prevention and clinical treatment of tuberculosis.

Paenibacillus ferrarius sp. nov., isolated from iron mineral soil.

A Gram-reaction-positive, endospore-forming, aerobic bacterium, designated strain CY1(T), was isolated from iron mineral soil of Hunan Province, China. The isolate was rod-shaped and motile by means of peritrichous flagella. The major cellular fatty acids were anteiso-C15:0 and iso-C16:0 and the major quinone was menaquinone 7. The major polar lipids were phosphatidylglycerol and diphosphatidylglycerol phosphatidylethanolamine. The genomic DNA G+C content was 50.5 mol% and the major diagnostic diamino acid in cell-wall peptidoglycan was meso-diaminopimelic acid. Phylogenetic analyses based on the 16S rRNA gene sequence indicated that strain CY1(T) is most closely related to Paenibacillus chondroitinus DSM 5051(T) (97.7% 16S rRNA gene sequence similarity), Paenibacillus pocheonensis Gsoil 1138(T) (97.4%) and Paenibacillus frigoriresistens YIM 016(T) (97.0%). DNA-DNA hybridization dissociation values were lower than 49% with the most closely related species. On the basis of phenotypic, chemotaxonomic and phylogenetic evidence, strain CY1(T) is affiliated to the genus Paenibacillus, but could be distinguished from the species of this genus. A novel species with the name Paenibacillus ferrarius sp. nov. is proposed. The type strain is CY1(T) ( =KCTC 33419(T) =CCTCC AB 2013369(T)).

How does climate change affect potential yields of four staple grain crops worldwide by 2030?

Global food security basically depends on potential yields of staple grain crops worldwide, especially under climate change. However, most scholars use various models of production function in which climatic factors are often considered to estimate crop yield mostly at local or regional level. Therefore, in this paper: Potential yields of rice, wheat, maize and soybean worldwide by 2030 are projected creatively using Auto-regressive Integrated Moving Average and Trend Regressed (ARIMA-TR) model in which actual yields in recent two years are used for testing the reliability of projection and Gray System (GS) model for validating the test; Especially individual impacts of climate change on the productions of rice, wheat, maize and soybean worldwide since 1961 are analyzed by using unary regression model in which global mean temperature and land precipitation are independent variable while the yield of crop being dependent one, respectively. Results show that: by 2030, the ratio between average and top yields of world rice is projected to be 50.6% increasing, while those of world wheat, world maize and world soybean are projected to be 38.0% increasing, 14.7% decreasing and 72.5% increasing, respectively. Since 1961 global warming has exerted a negative impact on average yield of world rice less than on its top, a positive effect on average yield of world wheat while a negative impact on its top, a positive effect on average yield of world maize less than on its top, and a positive influence on average yield of world soybean while a negative one on its top, which might be slightly mitigated by 'Carbon Peak' target. The fluctuation of global rainfall contributes to the productions of these crops much less than global warming during same period. Our findings indicate that: to improve global production of four staple grain crops by 2030, the priorities of input should be given to either rice or wheat in both high and low yield countries, whereas to maize in high yield countries and to soybean in low yield countries. These insights highlight some difference from previous studies, and provide academia with innovative comprehension and policy-decision makers with supportive information on sustainable production of these four staple grain crops for global food security under climate change in the future.

Pyrenecarboxaldehyde@Graphene Oxide Acted as a Highly Efficient ECL Emitter and Target-Triggered the Recyclable Cascade System as an Amplifier for Ultrasensitive APE1 Activity Detection.

Herein, pyrenecarboxaldehyde@graphene oxide (Pyc@GO) sheets with highly efficient electrochemiluminescence (ECL) as emitters were prepared by a noncovalent combination to develop a neoteric ECL biosensing platform for the ultrasensitive assessment of human apurinic/apyrimidinic endonuclease1 (APE1) activity. Impressively, the pyrenecarboxaldehyde (Pyc) molecules were able to form stable polar functional groups on the surface of GO sheets through the noncovalent π-π stacking mechanism to prevent intermolecular restacking and simultaneously generate Pyc@GO sheets. Compared with the tightly packed PAH nanocrystals, the Pyc@GO sheets significantly reduced internal filtering effects and diminished nonactivated emitters to enhance ECL intensity and achieve strong ECL emission. Furthermore, the APE1-activated initiators could trigger the recyclable cascade amplified system based on the synergistic cross-activation between catalytic hairpin assembly (CHA) and DNAzyme, which improved the signal amplification and transduction ability. Consequently, the developed ECL platform for the detection of APE1 activity displayed exceptional sensitivity with a low detection limit of 4.6 × 10-9 U·mL-1 ranging from 10-8 to 10-2 U·mL-1. Therefore, the proposed strategy holds great promise for the future development of sensitive and reliable biosensing platforms for the detection of various biomarkers.