Spatiotemporal heterogeneity and long-term impact of meteorological, environmental, and socio-economic factors on scrub typhus in China from 2006 to 2018.

BACKGROUND: Large-scale outbreaks of scrub typhus combined with its emergence in new areas as a vector-borne rickettsiosis highlight the ongoing neglect of this disease. This study aims to explore the long-term changes and regional leading factors of scrub typhus in China, with the goal of providing valuable insights for disease prevention and control. METHODS: This study utilized a Bayesian space-time hierarchical model (BSTHM) to examine the spatiotemporal heterogeneity of scrub typhus and analyze the relationship between environmental factors and scrub typhus in southern and northern China from 2006 to 2018. Additionally, a GeoDetector model was employed to assess the predominant influences of geographical and socioeconomic factors in both regions. RESULTS: Scrub typhus exhibits a seasonal pattern, typically occurring during the summer and autumn months (June to November), with a peak in October. Geographically, the high-risk regions, or hot spots, are concentrated in the south, while the low-risk regions, or cold spots, are located in the north. Moreover, the distribution of scrub typhus is influenced by environment and socio-economic factors. In the north and south, the dominant factors are the monthly normalized vegetation index (NDVI) and temperature. An increase in NDVI per interquartile range (IQR) leads to a 7.580% decrease in scrub typhus risk in northern China, and a 19.180% increase in the southern. Similarly, of 1 IQR increase in temperature reduces the risk of scrub typhus by 10.720% in the north but increases it by 15.800% in the south. In terms of geographical and socio-economic factors, illiteracy rate and altitude are the key determinants in the respective areas, with q-values of 0.844 and 0.882. CONCLUSIONS: These results indicated that appropriate climate, environment, and social conditions would increase the risk of scrub typhus. This study provided helpful suggestions and a basis for reasonably allocating resources and controlling the occurrence of scrub typhus.

Liquid-Phase Dehydration of Glycerol to Acrolein with ZSM-5-Based Catalysts in the Presence of a Dispersing Agent.

Liquid-phase dehydration of glycerol to acrolein was investigated with solid acid catalysts, including H-ZSM-5, H3PO4-modified H-ZSM-5, H3PW12O40·14H2O and Cs2.5H0.5PW12O40, in the presence of sulfolane ((CH2)4SO2) as a dispersing agent under atmospheric pressure N2 in a batch reactor. High weak-acidity H-ZSM-5, high temperatures and high-boiling-point sulfolane improved the activity and selectivity for the production of acrolein through suppressing the formation of polymers and coke and promoting the diffusion of glycerol and products. Brønsted acid sites were soundly demonstrated to be responsible for dehydration of glycerol to acrolein by infrared spectroscopy of pyridine adsorption. Brønsted weak acid sites favored the selectivity to acrolein. Combined catalytic and temperature-programmed desorption of ammonia studies revealed that the selectivity to acrolein increased as the weak-acidity increased over the ZSM-5-based catalysts. The ZSM-5-based catalysts produced a higher selectivity to acrolein, while the heteropolyacids resulted in a higher selectivity to polymers and coke.

Structure and physicochemical properties of low digestible Euryale ferox Salisb. seed starch.

BACKGROUND: Euryale ferox Salisb. is widely grown in China and Southeast Asia as a grain crop and medicinal plant. The composition, morphology, structure, physicochemical properties, thermal properties, and in vitro digestibility of North Euryale ferox seeds starch (NEFS), hybrid Euryale ferox seeds starch (HEFS), and South Euryale ferox seeds starch (SEFS) were studied. RESULT: Of the varieties that were studied, the amylose content of NEFS (23.03%) was the highest. Starch granules of each variety were smooth, sharp, small, and had an average diameter of 2 µm. All three varieties were A-type crystals with crystallinity ranging from 26.42% to 28.17%. The degree of double helix and the short-range order ranged from 1.9006 to 2.5324 and 1.4294 to 1.6006, respectively. The high proportion of C1 region in NEFS (17.74%) and HEFS (17.66%) were found. Thermodynamic properties in North Euryale ferox seeds included the highest onset temperature (To ) (71.43 °C), peak temperature (Tp ) (76.60 °C), conclusion temperature (Tc ) (82.77 °C), enthalpy of gelatinization (ΔH) (12.64 J g-1 ), and peak viscosity (1514 mPa·s). All three varieties maintained a low level of in vitro digestibility, with the highest resistant starch (RS) content (29.57%), the lowest rapidly digestible starch (RDS) content (27.07%), and the slowest hydrolysis kinetic constant (0.0303) in NEFS. CONCLUSION: The results revealed that the low digestibility of NEFS was attributable to compact granules, high crystallinity, high degree of order, and strong thermal stability. These digestive, physicochemical, and thermodynamic properties provide information for the future application of Euryale ferox seed starch in the food industry. © 2022 Society of Chemical Industry.

A Supported Pd2 Dual-Atom Site Catalyst for Efficient Electrochemical CO2 Reduction.

Dual-atom site catalysts (DACs) have emerged as a new frontier in heterogeneous catalysis because the synergistic effect between adjacent metal atoms can promote their catalytic activity while maintaining the advantages of single-atom site catalysts (SACs), like 100 % atomic utilization efficiency and excellent selectivity. Herein, a supported Pd2 DAC was synthesized and used for electrochemical CO2 reduction reaction (CO2 RR) for the first time. The as-obtained Pd2 DAC exhibited superior CO2 RR catalytic performance with 98.2 % CO faradic efficiency at -0.85 V vs. RHE, far exceeding that of Pd1 SAC, and coupled with long-term stability. The density functional theory (DFT) calculations revealed that the intrinsic reason for the superior activity of Pd2 DAC toward CO2 RR was the electron transfer between Pd atoms at the dimeric Pd sites. Thus, Pd2 DAC possessed moderate adsorption strength of CO*, which was beneficial for CO production in CO2 RR.

Silver Single-Atom Catalyst for Efficient Electrochemical CO2 Reduction Synthesized from Thermal Transformation and Surface Reconstruction.

We report an Ag1 single-atom catalyst (Ag1 /MnO2 ), which was synthesized from thermal transformation of Ag nanoparticles (NPs) and surface reconstruction of MnO2 . The evolution process of Ag NPs to single atoms is firstly revealed by various techniques, including in situ ETEM, in situ XRD and DFT calculations. The temperature-induced surface reconstruction process from the MnO2 (211) to (310) lattice plane is critical to firmly confine the existing surface of Ag single atoms; that is, the thermal treatment and surface reconstruction of MnO2 is the driving force for the formation of single Ag atoms. The as-obtained Ag1 /MnO2 achieved 95.7 % Faradic efficiency at -0.85 V vs. RHE, and coupled with long-term stability for electrochemical CO2 reduction reaction (CO2 RR). DFT calculations indicated single Ag sites possessed high electronic density close to Fermi Level and could act exclusively as the active sites in the CO2 RR. As a result, the Ag1 /MnO2 catalyst demonstrated remarkable performance for the CO2 RR, far surpassing the conventional Ag nanosized catalyst (AgNP /MnO2 ) and other reported Ag-based catalysts.

Preference of blood pressure measurement methods by primary care doctors in Hong Kong: a cross-sectional survey.

BACKGROUND: Hypertension is the most common chronic disease and is the leading cause of morbidity and mortality. Its screening, diagnosis, and management depend heavily on accurate blood pressure (BP) measurement. It is recommended that the diagnosis of hypertension should be confirmed or corroborated by out-of-office BP values, measured using ambulatory BP monitoring (ABPM) and home BP monitoring (HBPM). When office BP is used, automated office BP (AOBP) measurement method, which automatically provides an average of 3-5 BP readings, should be preferred. This study aimed to describe the BP measurement methods commonly used by doctors in primary care in Hong Kong, to screen, diagnose, and manage hypertensive patients. METHODS: In this cross-sectional survey, all doctors registered in the Hong Kong "Primary Care Directory" were mailed a questionnaire, asking their preferred BP-measuring methods to screen, diagnose, and manage hypertensive patients. Furthermore, we also elicited information on the usual number of office BP or HBPM readings obtained, to diagnose or manage hypertension. RESULTS: Of the 1738 doctors included from the directory, 445 responded. Manual measurement using a mercury or aneroid device was found to be the commonest method to screen (63.1%), diagnose (56.4%), and manage (72.4%) hypertension. There was a significant underutilisation of ABPM, with only 1.6% doctors using this method to diagnose hypertension. HBPM was used by 22.2% and 56.8% of the respondents to diagnose and manage hypertension, respectively. A quarter (26.7%) of the respondents reported using only one in-office BP reading, while around 40% participants reported using ≥12 HBPM readings. Doctors with specialist qualification in family medicine were more likely to use AOBP in clinics and to obtain the recommended number of office BP readings for diagnosis and management of hypertension. CONCLUSION: Primary Care doctors in Hong Kong prefer to use manual office BP values, measured using mercury or aneroid devices, to screen, diagnose, and manage hypertension, highlighting a marked underutilisation of AOBP and out-of-office BP measuring techniques, especially that of ABPM. Further studies are indicated to understand the underlying reasons and to minimise the gap between real-life clinical practice and those recommended, based on scientific advances. TRIAL REGISTRATION: Clinicaltrial.gov; ref. no.: NCT03926897.

Highly Efficient Electroreduction of CO2 on Nickel Single-Atom Catalysts: Atom Trapping and Nitrogen Anchoring.

Construction of single atom catalysts (SACs) with high activity toward electroreduction of CO2 still remains a great challenge. A very simple and truly cost-effective synthetic strategy is proposed to prepare SACs via a impregnation-pyrolysis method, through one-step pyrolysis of graphene oxide aerogel. Compared with other traditional methods, this process is fast and free of repeated acid etching, and thus it has great potential for facile operation and large-scale manufacturing. Both X-ray absorption fine structure and high-angle annular dark-field scanning transmission electron microscopy images confirm the presence of isolated nickel atoms, with a high Ni loading of ≈2.6 wt%. The obtained 3D porous Ni- and N-codoped graphene aerogel exhibits excellent activity toward electroreduction of CO2 to CO, in particular exhibiting a remarkable CO Faradaic efficiency of 90.2%. Density functional theory calculations reveal that free energies for the formation of intermediate *COOH on coordinatively unsaturated NiN sites are significantly lower than that on NiN4 site, suggesting the outstanding activities of CO2 electroreduction originate from coordinatively unsaturated NiN sites in catalysts.

Electrochemical Reduction of Carbon Dioxide to Value-Added Products: The Electrocatalyst and Microbial Electrosynthesis.

The electrochemical reduction of carbon dioxide (CO2 ) to value-added products obtains great attention and investigation worldwide in recent years. The commercialization of this green process relies on the progress of relating high-performance electrocatalysts and their feasibility with proper reactor design. The microbial electrosynthesis (MES) is an alternative route to reduce CO2 with electroactive bio-film electrode as catalyst. This review presents the research status and development of cathode catalysts, particularly focusing on the active sites and development tendency, for highly efficient electrochemical reduction CO2 from personal viewpoint. Some of our results are also presented to exhibit contributions. MES shows a similar process to the typical electrochemical reduction of CO2 . Their combination is an important trend, and the future research in this field is full of challenges and opportunities.

Establishing an innovative carbohydrate metabolic pathway for efficient production of 2-keto-L-gulonic acid in Ketogulonicigenium robustum initiated by intronic promoters.

BACKGROUND: 2-Keto-L-gulonic acid (2-KGA), the precursor of vitamin C, is currently produced by two-step fermentation. In the second step, L-sorbose is transformed into 2-KGA by the symbiosis system composed of Ketogulonicigenium vulgare and Bacillus megaterium. Due to the different nutrient requirements and the uncertain ratio of the two strains, the symbiosis system significantly limits strain improvement and fermentation optimization. RESULTS: In this study, Ketogulonicigenium robustum SPU_B003 was reported for its capability to grow well independently and to produce more 2-KGA than that of K. vulgare in a mono-culture system. The complete genome of K. robustum SPU_B003 was sequenced, and the metabolic characteristics were analyzed. Compared to the four reported K. vulgare genomes, K. robustum SPU_B003 contained more tRNAs, rRNAs, NAD and NADP biosynthetic genes, as well as regulation- and cell signaling-related genes. Moreover, the amino acid biosynthesis pathways were more complete. Two species-specific internal promoters, P1 (orf_01408 promoter) and P2 (orf_02221 promoter), were predicted and validated by detecting their initiation activity. To efficiently produce 2-KGA with decreased CO2 release, an innovative acetyl-CoA biosynthetic pathway (XFP-PTA pathway) was introduced into K. robustum SPU_B003 by expressing heterologous phosphoketolase (xfp) and phosphotransacetylase (pta) initiated by internal promoters. After gene optimization, the recombinant strain K. robustum/pBBR-P1_xfp2502-P2_pta2145 enhanced acetyl-CoA approximately 2.4-fold and increased 2-KGA production by 22.27% compared to the control strain K. robustum/pBBR1MCS-2. Accordingly, the transcriptional level of the 6-phosphogluconate dehydrogenase (pgd) and pyruvate dehydrogenase genes (pdh) decreased by 24.33 ± 6.67 and 8.67 ± 5.51%, respectively. The key genes responsible for 2-KGA biosynthesis, sorbose dehydrogenase gene (sdh) and sorbosone dehydrogenase gene (sndh), were up-regulated to different degrees in the recombinant strain. CONCLUSIONS: The genome-based functional analysis of K. robustum SPU_B003 provided a new understanding of the specific metabolic characteristics. The new XFP-PTA pathway was an efficient route to enhance acetyl-CoA levels and to therefore promote 2-KGA production.

Nitrogen-Doped Graphene Quantum Dots Enhance the Activity of Bi2 O3 Nanosheets for Electrochemical Reduction of CO2 in a Wide Negative Potential Region.

Large numbers of catalysts have been developed for the electrochemical reduction of CO2 to value-added liquid fuels. However, it remains a challenge to maintain a high current efficiency in a wide negative potential range for achieving a high production rate of the target products. Herein, we report a 2D/0D composite catalyst composed of bismuth oxide nanosheets and nitrogen-doped graphene quantum dots (Bi2 O3 -NGQDs) for highly efficient electrochemical reduction of CO2 to formate. Bi2 O3 -NGQDs demonstrates a nearly 100 % formate Faraday efficiency (FE) at a moderate overpotential of 0.7 V with a good stability. Strikingly, Bi2 O3 -NGQDs exhibit a high activity (average formate FE of 95.6 %) from -0.9 V to -1.2 V vs. RHE. Additionally, DFT calculations reveal that the origin of enhanced activity in this wide negative potential range can be attributed to the increased adsorption energy of CO2 (ads) and OCHO* intermediate after combination with NGQDs.

[Exploring correlation between molecular state and nanofiltration mass transfer process of synephrine from Citrus aurantium].

Based on the solution-diffusion effect and the charge effect theory in nanofiltration separation, the correlation between initial concentration and mass transfer coefficient was constructed to establish a mathematic model of synephrine in mass transfer process and verify its applicability. The experimental results showed that there was a linear relationship between operation pressure and membrane flux. Meanwhile, the membrane flux was gradually decayed with the increase of solute concentration. Besides, mass transfer coefficient and initial concentration of synephrine showed power function correlation with each other by solution-diffusion effect and the charge effect, and the regression coefficients were greater than 0.9. The mass transfer coefficient of dissociation synephrine was less than that in the state of free and free-dissociation. Moreover, on the basis of power function relationship between mass transfer coefficient and initial concentration, the results showed that the predicted rejections of synephrine from Citrus aurantium water extract by use of the mathematical model approximated well to real ones, verifying that the model was practical and feasible. The unclear separation mechanism of nanofiltration for alkaloids was clarified preliminary by the predicted model of nanofiltration separation with synephrine as the example, providing theoretical and technical support for nanofiltration separation, especially for traditional Chinese medicine with alkaloids.

[Analyze nanofiltration separation rule of chlorogenic acid from low concentration ethanol by Donnan effect and solution-diffusion effect].

To separate chlorogenic acid from low concentration ethanol and explore the influence of Donnan effect and solution-diffusion effect on the nanofiltration separation rule. The experiment showed that solution pH and ethanol volume percent had influences on the separation of chlorogenic acid. Within the pH values from 3 to 7 for chlorogenic acid in 30% ethanol, the rejection rate of chlorogenic acid was changed by 70.27%. Through the response surface method for quadratic regression model, an interaction had been found in molecule weight cut-off, pH and ethanol volume percent. In fixed nanofiltration apparatus, the existence states of chlorogenic acid determinedits separation rules. With the increase of ethanol concentration, the free form chlorogenic acid was easily adsorbed, dissolved on membrane surface and then caused high transmittance due to the solution-diffusion effect. However, at the same time, due to the double effects of Donnan effect and solution-diffusion effect, the ionic state of chlorogenic acid was hard to be adsorbed in membrane surface and thus caused high rejection rate. The combination of Box-Behnken design and response surface analysis can well optimize the concentrate process by nanofiltration, and the results showed that nanofiltration had several big advantages over the traditional vacuum concentrate technology, meanwhile, and solved the problems of low efficiency and serious component lossesin the Chinese medicines separation process for low concentration organic solvent-water solution.

Detection of Echinoderm Microtubule Associated Protein Like 4-Anaplastic Lymphoma Kinase Fusion Genes in Non-small Cell Lung Cancer Clinical Samples by a Real-time Quantitative Reverse Transcription Polymerase Chain Reaction Method.

Objective To establish a real-time quantitative reverse transcription polymerase chain reaction assay (qRT-PCR) for the rapid, sensitive, and specific detection of echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion genes in non-small cell lung cancer. Methods The specific primers for the four variants of EML4-ALK fusion genes (V1, V2, V3a, and V3b) and Taqman fluorescence probes for the detection of the target sequences were carefully designed by the Primer Premier 5.0 software. Then, using pseudovirus containing EML4-ALK fusion genes variants (V1, V2, V3a, and V3b) as the study objects, we further analyzed the lower limit, sensitivity, and specificity of this method. Finally, 50 clinical samples, including 3 ALK-fluorescence in situ hybridization (FISH) positive specimens, were collected and used to detect EML4-ALK fusion genes using this method. Results The lower limit of this method for the detection of EML4-ALK fusion genes was 10 copies/µl if no interference of background RNA existed. Regarding the method's sensitivity, the detection resolution was as high as 1% and 0.5% in the background of 500 and 5000 copies/µl wild-type ALK gene, respectively. Regarding the method's specificity, no non-specific amplification was found when it was used to detect EML4-ALK fusion genes in leukocyte and plasma RNA samples from healthy volunteers. Among the 50 clinical samples, 47 ALK-FISH negative samples were also negative. Among 3 ALK-FISH positive samples, 2 cases were detected positive using this method, but another was not detected because of the failure of RNA extraction. Conclusion The proposed qRT-PCR assay for the detection of EML4-ALK fusion genes is rapid, simple, sensitive, and specific, which is deserved to be validated and widely used in clinical settings.

Human-to-human transmission of severe fever with thrombocytopenia syndrome bunyavirus through contact with infectious blood.

We investigated an outbreak of severe fever with thrombocytopenia syndrome (SFTS) that occurred during May and June 2010, to identify the mode of transmission. Contact with the index patient's blood was significantly associated with development of SFTS (P = .01, by the χ(2) test for linear trend); the frequency of contact with the index patient's blood increased the risk of SFTS in a dose-response manner (P = .03, by the χ(2) test for linear trend). We concluded that human-to-human transmission caused this cluster of cases.

Epidemic Characteristics and Meteorological Risk Factors of Hemorrhagic Fever With Renal Syndrome in 151 Cities in China From 2015 to 2021: Retrospective Analysis.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) continues to pose a significant public health threat to the population in China. Previous epidemiological evidence indicates that HFRS is climate sensitive and influenced by meteorological factors. However, past studies either focused on too-narrow geographical regions or investigated time periods that were too early. There is an urgent need for a comprehensive analysis to interpret the epidemiological patterns of meteorological factors affecting the incidence of HFRS across diverse climate zones. OBJECTIVE: In this study, we aimed to describe the overall epidemic characteristics of HFRS and explore the linkage between monthly HFRS cases and meteorological factors at different climate levels in China. METHODS: The reported HFRS cases and meteorological data were collected from 151 cities in China during the period from 2015 to 2021. We conducted a 3-stage analysis, adopting a distributed lag nonlinear model and a generalized additive model to estimate the interactions and marginal effects of meteorological factors on HFRS. RESULTS: This study included a total of 63,180 cases of HFRS; the epidemic trends showed seasonal fluctuations, with patterns varying across different climate zones. Temperature had the greatest impact on the incidence of HFRS, with the maximum hysteresis effects being at 1 month (-19 ºC; relative risk [RR] 1.64, 95% CI 1.24-2.15) in the midtemperate zone, 0 months (28 ºC; RR 3.15, 95% CI 2.13-4.65) in the warm-temperate zone, and 0 months (4 ºC; RR 1.72, 95% CI 1.31-2.25) in the subtropical zone. Interactions were discovered between the average temperature, relative humidity, and precipitation in different temperature zones. Moreover, the influence of precipitation and relative humidity on the incidence of HFRS had different characteristics under different temperature layers. The hysteresis effect of meteorological factors did not end after an epidemic season, but gradually weakened in the following 1 or 2 seasons. CONCLUSIONS: Weather variability, especially low temperature, plays an important role in epidemics of HFRS in China. A long hysteresis effect indicates the necessity of continuous intervention following an HFRS epidemic. This finding can help public health departments guide the prevention and control of HFRS and develop strategies to cope with the impacts of climate change in specific regions.

Tuberculosis-targeted next-generation sequencing and machine learning: An ultrasensitive diagnostic strategy for paucibacillary pulmonary tuberculosis and tuberculous meningitis.

BACKGROUND: Existing diagnostic approaches for paucibacillary tuberculosis (TB) are limited by the low sensitivity of testing methods and difficulty in obtaining suitable samples. METHODS: An ultrasensitive TB diagnostic strategy was established, integrating efficient and specific TB targeted next-generation sequencing and machine learning models, and validated in clinical cohorts to test plasma cfDNA, cerebrospinal fluid (CSF) DNA collected from tuberculous meningitis (TBM) and pediatric pulmonary TB (PPTB) patients. RESULTS: In the detection of 227 samples, application of the specific thresholds of CSF DNA (AUC = 0.974) and plasma cfDNA (AUC = 0.908) yielded sensitivity of 97.01 % and the specificity of 95.65 % in CSF samples and sensitivity of 82.61 % and specificity of 86.36 % in plasma samples, respectively. In the analysis of 44 paired samples from TBM patients, our strategy had a high concordance of 90.91 % (40/44) in plasma cfDNA and CSF DNA with both sensitivity of 95.45 % (42/44). In the PPTB patient, the sensitivity of the TB diagnostic strategy yielded higher sensitivity on plasma specimen than Xpert assay on gastric lavage (28.57 % VS. 15.38 %). CONCLUSIONS: Our TB diagnostic strategy provides greater detection sensitivity for paucibacillary TB, while plasma cfDNA as an easily collected specimen, could be an appropriate sample type for PTB and TBM diagnosis.

The Intersection of cerebral cholesterol metabolism and Alzheimer's disease: Mechanisms and therapeutic prospects.

Alzheimer's disease (AD) is a common neurodegenerative disease in the elderly, the exact pathogenesis of which remains incompletely understood, and effective preventive and therapeutic drugs are currently lacking. Cholesterol plays a vital role in cell membrane formation and neurotransmitter synthesis, and its abnormal metabolism is associated with the onset of AD. With the continuous advancement of imaging techniques and molecular biology methods, researchers can more accurately explore the relationship between cholesterol metabolism and AD. Elevated cholesterol levels may lead to vascular dysfunction, thereby affecting neuronal function. Additionally, abnormal cholesterol metabolism may affect the metabolism of ß-amyloid protein, thereby promoting the onset of AD. Brain cholesterol levels are regulated by multiple factors. This review aims to deepen the understanding of the subtle relationship between cholesterol homeostasis and AD, and to introduce the latest advances in cholesterol-regulating AD treatment strategies, thereby inspiring readers to contemplate deeply on this complex relationship. Although there are still many unresolved important issues regarding the risk of brain cholesterol and AD, and some studies may have opposite conclusions, further research is needed to enrich our understanding. However, these findings are expected to deepen our understanding of the pathogenesis of AD and provide important insights for the future development of AD treatment strategies targeting brain cholesterol homeostasis.

Knowledge-guided machine learning can improve carbon cycle quantification in agroecosystems.

Accurate and cost-effective quantification of the carbon cycle for agroecosystems at decision-relevant scales is critical to mitigating climate change and ensuring sustainable food production. However, conventional process-based or data-driven modeling approaches alone have large prediction uncertainties due to the complex biogeochemical processes to model and the lack of observations to constrain many key state and flux variables. Here we propose a Knowledge-Guided Machine Learning (KGML) framework that addresses the above challenges by integrating knowledge embedded in a process-based model, high-resolution remote sensing observations, and machine learning (ML) techniques. Using the U.S. Corn Belt as a testbed, we demonstrate that KGML can outperform conventional process-based and black-box ML models in quantifying carbon cycle dynamics. Our high-resolution approach quantitatively reveals 86% more spatial detail of soil organic carbon changes than conventional coarse-resolution approaches. Moreover, we outline a protocol for improving KGML via various paths, which can be generalized to develop hybrid models to better predict complex earth system dynamics.

Restriction endonuclease-mediated real-time digestion-PCR for somatic mutation detection.

PCR is a powerful platform for clinical and diagnostic applications, but challenges remain in detecting somatic mutations, as mutant cells are often mixed with more numerous wild-type cells at the tissue-sample sites. Here, we describe a novel method that couples PCR with restriction endonuclease digestion (designated real-time digestion-PCR, or RTD-PCR) in a one-step reaction tube for detecting somatic mutations from a minority of cells. The PCR mixture contains a thermostable restriction enzyme that digests wild-type alleles during the PCR program, allowing selective amplification of the mutant alleles. To validate this method, we used real-time digestion-PCR for the specific detection of the EGFR (epidermal growth factor receptor) treatment resistance-inducing mutation, T790M, combining with three different platforms: Sanger sequencing, TaqMan probe PCR and Sequenom MassArray. From 78 clinical samples, seven T790M mutations were consistently detected on all three platforms, indicating that RTD-PCR may be a useful clinical tool for analyzing the T790M point mutation.

Metagenomic analysis of fever, thrombocytopenia and leukopenia syndrome (FTLS) in Henan Province, China: discovery of a new bunyavirus.

Since 2007, many cases of fever, thrombocytopenia and leukopenia syndrome (FTLS) have emerged in Henan Province, China. Patient reports of tick bites suggested that infection could contribute to FTLS. Many tick-transmitted microbial pathogens were tested for by PCR/RT-PCR and/or indirect immunofluorescence assay (IFA). However, only 8% (24/285) of samples collected from 2007 to 2010 tested positive for human granulocytic anaplasmosis (HGA), suggesting that other pathogens could be involved. Here, we used an unbiased metagenomic approach to screen and survey for microbes possibly associated with FTLS. BLASTx analysis of deduced protein sequences revealed that a novel bunyavirus (36% identity to Tehran virus, accession: HQ412604) was present only in sera from FTLS patients. A phylogenetic analysis further showed that, although closely related to Uukuniemi virus of the Phlebovirus genus, this virus was distinct. The candidate virus was examined for association with FTLS among samples collected from Henan province during 2007-2010. RT-PCR, viral cultures, and a seroepidemiologic survey were undertaken. RT-PCR results showed that 223 of 285 (78.24%) acute-phase serum samples contained viral RNA. Of 95 patients for whom paired acute and convalescent sera were available, 73 had serologic evidence of infection, with 52 seroconversions and 21 exhibiting a 4-fold increase in antibody titer to the virus. The new virus was isolated from patient acute-phase serum samples and named Henan Fever Virus (HNF virus). Whole-genome sequencing confirmed that the virus was a novel bunyavirus with genetic similarity to known bunyaviruses, and was most closely related to the Uukuniemi virus (34%, 24%, and 29% of maximum identity, respectively, for segment L, M, S at maximum query coverage). After the release of the GenBank sequences of SFTSV, we found that they were nearly identical (>99% identity). These results show that the novel bunyavirus (HNF virus) is strongly correlated with FTLS.