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Abstract Background Understanding the complex interactions between genes and their causal effects on diseases is crucial for developing targeted treatments and gaining insight into biological mechanisms. However, the analysis of molecular networks, especially in the context of high-dimensional data, presents significant challenges. Methods This study introduces MRdualPC, a computationally tractable algorithm based on the MRPC approach, to infer large-scale causal molecular networks. We apply MRdualPC to investigate the upstream causal transcriptomics influencing hypertension using a comprehensive dataset of kidney genome and transcriptome data. Results Our algorithm proves to be 100 times faster than MRPC on average in identifying transcriptomics drivers of hypertension. Through clustering, we identify 63 modules with causal driver genes, including 17 modules with extensive causal networks. Notably, we find that genes within one of the causal networks are associated with the electron transport chain and oxidative phosphorylation, previously linked to hypertension. Moreover, the identified causal ancestor genes show an over-representation of blood pressure-related genes. Conclusions MRdualPC has the potential for broader applications beyond gene expression data, including multi-omics integration. While there are limitations, such as the need for clustering in large gene expression datasets, our study represents a significant advancement in building causal molecular networks, offering researchers a valuable tool for analyzing big data and investigating complex diseases.

Abstract Many chemical transport models treat mineral dust as spherical. Solar backscatter retrievals of trace gases (e.g., OMI and TROPOMI) implicitly treat mineral dust as spherical. The impact of the morphology of mineral dust particles is studied to assess its implications for global chemical transport model (GEOS‐Chem) simulations and solar backscatter trace gas retrievals at ultraviolet and visible (UV‐Vis) wavelengths. We investigate how the morphology of mineral dust particles affects the simulated dust aerosol optical depth; surface area, reaction, and diffusion parameters for heterogeneous chemistry; phase function, and scattering weights for air mass factor (AMF) calculations used in solar backscatter retrievals. We use a mixture of various aspect ratios of spheroids to model the dust optical properties and a combination of shape and porosity to model the surface area, reaction, and diffusion parameters. We find that assuming spherical particles can introduce size‐dependent and wavelength‐dependent errors of up to 14% in simulated dust extinction efficiency with corresponding error in simulated dust optical depth typically within 5%. We find that use of spheroids rather than spheres increases forward scattered radiance and decreases backward scattering that in turn decrease the sensitivity of solar backscatter retrievals of NO2 to aerosols by factors of 2.0–2.5. We develop and apply a theoretical framework based on porosity and surface fractal dimension with corresponding increase in the reactive uptake coefficient driven by increased surface area and species reactivity. Differences are large enough to warrant consideration of dust non‐sphericity for chemical transport models and UV‐Vis trace gas retrievals.

Small satellites are efficient at performing Earth science from space due to their limited cost and size. Small satellites (cubesats) achieve much with limited power production/storage, heat dissipation, data storage, and ground contact points/bandwidth. As such it is beneficial to offload as much as possible to ground support systems. Consider the HyperAngular Rainbow Polarimeter (HARP) Cubesat. Its goals were to serve as a technical demonstration prior to the development of HARP2 aboard the NASA Plankton Aerosol Cloud and ocean Ecosystem (PACE) mission and to serve as an Earth viewing remote sensing platform which measured the characteristics of clouds and aerosols. HARP cubesat was limited to taking 5-minute capture sequences once every 24 h. It took approximately 10 such captures before it needed to perform data downlink and have its memory cleared for continued use. A ground station at NASA Wallops supported HARP with approximately three points of contact each day. To maximize the value of each capture, ground support software was developed leveraging public data to inform the schedule of each capture. In this paper, we review the algorithms and data sources that allowed us to: 1; predict the HARP orbital track a week in advance, 2; predict also the location of other remote sensing satellites and ground stations relative to HARP, 3; predict the ground view geometry of the instrument along its orbital track, 4; compare global climatological data products of clouds and aerosols along the predicted orbital tracks, and 5; identify and integrate important ground target locations based on remote sensing literature and ongoing natural phenomena. This HARP Orbital Prediction System (HOPS) made HARP into a successful technical demonstration which also offered significant science value. The HOPS system presents a valuable methodology for small satellites to operate efficiently despite their limited capabilities. HOPS is also a useful testbed for studying the sensitivity of scene geometry. Using HOPS, we show that for a wide field-of-view (FOV) instrument, like HARP, latitude/longitude geolocation varies by approximately 0.1∘ at a height of 8–10 km. Scattering angles vary less than 0.01∘ at similar heights, with the worst performance near direct backscatter 180∘.

Abstract Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation. Imputation of kidney proteome and microRNAome uncovered 97 renal proteins and 11 miRNAs associated with BP. Integration with plasma proteomics and metabolomics illuminated circulating levels of myo-inositol, 4-guanidinobutanoate and angiotensinogen as downstream effectors of several kidney BP genes (SLC5A11, AGMAT, AGT, respectively). We showed that genetically determined reduction in renal expression may mimic the effects of rare loss-of-function variants on kidney mRNA/protein and lead to an increase in BP (e.g., ENPEP). We demonstrated a strong correlation (r = 0.81) in expression of protein-coding genes between cells harvested from urine and the kidney highlighting a diagnostic potential of urinary cell transcriptomics. We uncovered adenylyl cyclase activators as a repurposing opportunity for hypertension and illustrated examples of BP-elevating effects of anticancer drugs (e.g. tubulin polymerisation inhibitors). Collectively, our studies provide new biological insights into genetic regulation of BP with potential to drive clinical translation in hypertension.

The migration, transformation, and accumulation of dissolved organic matter (DOM) in pore water of sediment cores play a pivotal role in lacustrine carbon cycling. In order to understand the dynamics of DOM in the sediments of large shallow eutrophic lakes, we examined the vertical profiles of DOM and the benthic fluxes of dissolved organic carbon (DOC) in sediment cores located in algae accumulated, dredged, and central areas of eutrophic Lake Taihu, China. Optical properties showed the significant influence of terrestrial inputs on the DOM components of pore water in the algae accumulated area but an abundant accumulation of autochthonous DOM in the central area. The benthic fluxes of DOC ranging from −458.2 to −139.4 mg·m−2·d−1 in the algae accumulated area displayed an opposite diffusion direction to the other two areas. The flux ranges of 9.5–31.2 mg·m−2·d−1 in the dredged area and 14.6–48.0 mg·m−2·d−1 in the central area were relatively smaller than those in the previously reported lake ecosystems with low trophic levels. Dredging engineering disturbed the pre-dredging distribution patterns of DOM in sediment cores. The deposition, accumulation, and transformation of massive algae scums in eutrophic lakes probably promoted the humification degree of sediments. HIGHLIGHTS Terrestrial input significantly affected the dissolved organic matter (DOM) components of the algae accumulated area.; DOC diffusion direction of the algae accumulated area was opposite to the other areas.; Dredging work disturbed the pre-dredging distribution patterns of DOM in sediment cores.; Biogeochemical processes of accumulated algae scums probably promoted humification.;

Aerosol layer height (ALH) is an important but uncertain parameter for evaluating the impact of aerosols on weather and climate and for accurate atmospheric correction. This study aims to assess the potential for measuring ALH by the Ocean Color Instrument (OCI) on NASA’s Plankton, Aerosol, Cloud, ocean Ecosystem satellite. OCI measures Earth-reflected solar spectrum including reflectance in the oxygen (O2) A and B absorption bands that are invaluable for determining ALH. We assessed the sensitivity and information contained therein in retrieving ALH over the ocean surface by using the radiative transfer simulation of OCI observations in the O2 bands. The capabilities were also demonstrated using hyperspectral data measured by the TROPOspheric Monitoring Instrument (TROPOMI), as spectrally convolved into the OCI bands. Our results indicate that (a) OCI observations in the O2 A band are sensitive to ALH, whereas those around the O2 B band have relatively reduced sensitivity; (b) the most pronounced sensitivity to ALH is found in the 762.5 nm (and 690 nm) around the oxygen A (and B) bands, which are selected for ALH retrievals in this study; and (c) the ALH retrieved from OCI proxy data is in good agreement with the aerosol profile probed by CALIOP lidar. Overall, the ALH retrievals for both smoke and dust events exhibit a root mean square error of 0.49 km and 0.31 km, respectively, for the smoke and dust cases, aligning with the uncertainties of ALH as measured from the concurrent TROPOMI and the Earth Polychromatic Imaging Camera instruments. Therefore, this study suggests from OCI observations that we can generate ALH products with a well-characterized uncertainty. The technique and results presented in this study are suitable to develop a simple but robust ALH algorithm for OCI observations when the data become available.

Summary: Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p

Abstract The Orbital Hall effect, which originates from materials with weak spin-orbit coupling, has attracted considerable interest for spin-orbitronic applications. Here, we demonstrate the inverse effect of the orbital Hall effect and observe orbitronic terahertz emission in the Ti and Mn materials. Through spin-orbit transition in the ferromagnetic layer, the generated orbital current can be converted to charge current in the Ti and Mn layers via the inverse orbital Hall effect. Furthermore, the inserted W layer provides an additional conversion of the orbital-charge current in the Ti and Mn layers, significantly enhancing the orbitronic terahertz emission. Moreover, the orbitronic terahertz emission can be manipulated by cooperating with the inverse orbital Hall effect and the inverse spin Hall effect in the different sample configurations. Our results not only discover the physical mechanism of condensed matter physics but also pave the way for designing promising spin-orbitronic devices and terahertz emitters.

Abstract Manipulating spin polarization orientation is challenging but crucial for field-free spintronic devices. Although such manipulation has been demonstrated in a limited number of antiferromagnetic metal-based systems, the inevitable shunting effects from the metallic layer can reduce the overall device efficiency. In this study, we propose an antiferromagnetic insulator-based heterostructure NiO/Ta/Pt/Co/Pt for such spin polarization control without any shunting effect in the antiferromagnetic layer. We show that zero-field magnetization switching can be realized and is related to the out-of-plane component of spin polarization modulated by the NiO/Pt interface. The zero-field magnetization switching ratio can be effectively tuned by the substrates, in which the easy axis of NiO can be manipulated by the tensile or compressive strain from the substrates. Our work demonstrates that the insulating antiferromagnet based heterostructure is a promising platform to enhance the spin-orbital torque efficiency and achieve field-free magnetization switching, thus opening an avenue towards energy-efficient spintronic devices.

Abstract The multi‐spectral satellite sensors such as MODIS have a large swath, high spatial resolution, and well onboard calibration, enabling aerosol retrievals with daily global coverage. Despite numerous available bands, MODIS aerosol algorithms over land typically only utilize measurements from 2 to 3 spectral wavelengths to retrieve Aerosol Optical Depth (AOD) based on prescribed aerosol models. To make full use of multi‐spectral measurements and prior information, we developed an aerosol algorithm based on physics‐informed deep learning (PDL) approach. With physical constraint from radiative transfer simulation, PDL can construct model functions between the whole spectral measurements and each retrieved aerosol parameter separately. AERONET validations in eastern China show that MODIS PDL algorithm can accurately retrieve AOD and fine AOD (R = 0.936) at 1 km resolution and has reliable performance in coarse AOD as well as notable sensitivity to aerosol absorption. The flexible and efficient PDL method provides a generalized algorithm for common multi‐spectral satellite measurements.

BackgroundThrough a survey and analysis of the population’s present state of health, it is possible to give data support for improving the health status of inhabitants in Naqu, Tibet. Additionally, it is possible to provide specific recommendations for the development of medical and healthcare facilities in Tibet.MethodsThe health scores of the participants were based on their responses to the four main sections of the questionnaire: dietary habits, living habits, health knowledge, and clinical disease history, and the variability of health status among groups with different characteristics was analyzed based on the scores. The four major sections were used to create classes of participants using latent class analysis (LCA). Using logistic regression, the factors influencing the classification of latent classes of health status were investigated.ResultsA total of 995 residents from 10 counties in Naqu were selected as the study subjects. And their demographic characteristics were described. The mean health score of residents after standardization was 81.59 ± 4.68. With the exception of gender, health scores differed between groups by age, education level, different occupations, marital status, and monthly income. The health status in Naqu, Tibet, was divided into two groups (entropy = 0.29, BLRT = 0.001, LMRT = 0.001) defined as the “good health group” and the “general health group.” A monthly income of more than ¥5000 adverse to good health in Naqu, Tibet.DiscussionSingle, well-educated young adults in Naqu, Tibet, have outstanding health. The vast majority of people in Tibet’s Naqu region were in good health. Furthermore, the population’s latent health status was divided into two classes, each with good dietary and living habits choices, low health knowledge, and a history of several clinical diseases. Univariate and multivariate logistic regression analysis showed that monthly income more than ¥5000 was an independent risk factor for poor health status.

Abstract Introduction Transbronchial lung biopsy (TBLB) is a relatively safe technique routinely employed by pulmonologists for the diagnosis of diffuse parenchymal lung disease (DPLD). Cryobiopsy is associated with higher diagnostic yield and a favorable risk/benefit ratio. Nevertheless, TBLB remains the representative method for definite diagnosis in developing countries. Objectives This study aimed to evaluate whether the results obtained from TBLB had clinical value to pulmonologists in the management of DPLD. Methods We performed a retrospective analysis of patients who underwent conventional TBLB for the diagnosis of DPLD from May 1, 2017, to April 30, 2019, at the Beijing Chao‐yang Hospital, Capital Medical University. The clinical value of TBLB was defined as leading to a specific histopathological diagnosis or being consistent with the clinical and radiological data. Results Seven hundred and forty‐three patients with suspected DPLD were recruited. Conventional TBLB was considered clinically valuable in 439 procedures (59.1%), including 360 cases provided with definitive histopathological diagnoses, and 79 cases that were consistent with the working diagnoses. Among the 439 cases of clinically valuable TBLBs, 88 (20.0%), 37, 77 (10.7%), and 61 (13.9%) cases were diagnosed as connective tissue disease‐related interstitial lung disease, definite histopathological diagnoses, malignancies, and nonspecific interstitial pneumonia, respectively. Conclusions Conventional TBLB served as a key determinant or provided supplementary information in the final diagnosis of non‐infectious DPLDs. TBLB decision‐making should therefore be based on clinical and radiological data.

IntroductionThe classification of the four tobacco shred varieties, tobacco silk, cut stem, expanded tobacco silk, and reconstituted tobacco shred, and the subsequent determination of tobacco shred components, are the primary tasks involved in calculating the tobacco shred blending ratio. The identification accuracy and subsequent component area calculation error directly affect the composition determination and quality of the tobacco shred. However, tiny tobacco shreds have complex physical and morphological characteristics; in particular, there is substantial similarity between the expanded tobacco silk and tobacco silk varieties, and this complicates their classification. There must be a certain amount of overlap and stacking in the distribution of tobacco shreds on the actual tobacco quality inspection line. There are 24 types of overlap alone, not to mention the stacking phenomenon. Self-winding does not make it easier to distinguish such varieties from the overlapped types, posing significant difficulties for machine vision-based tobacco shred classification and component area calculation tasks.MethodsThis study focuses on two significant challenges associated with identifying various types of overlapping tobacco shreds and acquiring overlapping regions to calculate overlapping areas. It develops a new segmentation model for tobacco shred images based on an improved Mask region-based convolutional neural network (RCNN). Mask RCNN is used as the segmentation network’s mainframe. Convolutional network and feature pyramid network (FPN) in the backbone are replaced with Densenet121 and U-FPN, respectively. The size and aspect ratios of anchors parameters in region proposal network (RPN) are optimized. An algorithm for the area calculation of the overlapped tobacco shred region (COT) is also proposed, which is applied to overlapped tobacco shred mask images to obtain overlapped regions and calculate the overlapped area.ResultsThe experimental results showed that the final segmentation accuracy and recall rates are 89.1% and 73.2%, respectively. The average area detection rate of 24 overlapped tobacco shred samples increases from 81.2% to 90%, achieving high segmentation accuracy and overlapped area calculation accuracy.DiscussionThis study provides a new implementation method for the type identification and component area calculation of overlapped tobacco shreds and a new approach for other similar overlapped image segmentation tasks.

BackgroundIn high altitude areas, like Tibet, most fetuses in breech presentation at term are delivered vaginally owing to a variety of reasons, but this has not been published.ObjectiveThis study aimed to provide references and evidence for the delivery of breach presentation term fetuses in high altitude areas, through comparing and analyzing the data of full-term singleton fetuses with breech or cephalic presentation in Naqu People’s Hospital, Tibet.Study designWe retrospectively analyzed the clinical data of 451 breech presentation fetuses mentioned above over a period of 5 years (2016–2020). A total of 526 cephalic presentation fetuses’ data within 3 months (1 June to 1 September 2020) of the same period were collected too. Statistics were compared and assembled on fetal mortality, Apgar scores, and severe neonatal complications for both planned cesarean section (CS) and vaginal delivery. In addition, we also analyzed the types of breech presentation, the second stage of labor, and damage to the maternal perineum during vaginal delivery.ResultsAmong the 451 cases of breech presentation fetuses, 22 cases (4.9%) elected for CS and 429 cases (95.1%) elected for vaginal delivery. Of the women who chose vaginal trial labor, 17 cases underwent emergency CSs. The perinatal and neonatal mortality rate was 4.2% in the planned vaginal delivery group and the incidence of severe neonatal complications was 11.7% in the transvaginal group, no deaths were detected in the CS group. Among the 526 cephalic control groups with planned vaginal delivery, the perinatal and neonatal mortality was 1.5% (p = 0.012), and the incidence of severe neonatal complications was 1.9%. Among vaginal breech deliveries, most of them were complete breech presentation (61.17%). Among the 364 cases, the proportion of intact perinea was 45.1%, and first degree lacerations accounted for 40.7%.ConclusionIn the Tibetan Plateau region, vaginal delivery was less safe than cephalic presentation fetuses for full-term breech presentation fetuses delivered in the lithotomy position. However, if dystocia or fetal distress can be identified in time and then encouraged to convert to cesarean, its safety will be greatly improved.

Objective: Multiple myeloma (MM) remains incurable with high rates of relapse. New therapeutic drugs are therefore urgently needed to improve the prognosis. JaponiconeA (JA), a natural product isolated from Inula japonica Thunb, has shown good anti-MM potential. A comprehensive study should therefore be conducted to identify both the in vitro and in vivo mechanisms of the anti-MM effects of JA. Methods: CCK8 assays and flow cytometry were used to detect the proliferation, apoptosis, and cell cycle of MM cell lines when treated with JA. In vivo experiments were conducted using subcutaneous xenograft mouse models. We also identified possible targets and the mechanism of JA using RNA-seq and c-Map databases, and identified the specific targets of JA in bortezomib-sensitive and -resistant MM cell lines using CETSA, DARTS, and rescue experiments. Furthermore, JA and bortezomib were used separately or together to characterize their possible synergistic effects. Results: In vitro, JA inhibited proliferation, and induced apoptosis and G2/M phase arrest in MM cell lines, and selectively killed primary CD138+ MM cells. In vivo, JA also demonstrated a strong anti-tumor effect with no observable toxicity. In addition, JA showed synergetic effects in combination with bortezomib, and enhanced the anti-tumor effect of bortezomib in bortezomib-resistant cells. CETSA and DARTS confirmed direct binding of JA to NF-κB inhibitor kinase beta (IKKβ), and overexpression of IKKβ or knockdown of IκBα partially rescued the apoptosis induced by JA. Conclusions: JA exhibited strong anti-tumor effects in MM. It sensitized myeloma cells to bortezomib and overcame NF-κB-induced drug resistance by inhibiting IKKβ, providing a new treatment strategy for MM patients.

Abstract Background Lung adenocarcinoma is the leading cause of cancer death worldwide. Recently, ubiquitin C-terminal hydrolase L1 (UCHL1) has been demonstrated to be highly expressed in many tumors and plays the role of an oncogene. However, the functional mechanism of UCHL1 is unclear in lung adenocarcinoma progression. Methods We analyzed the differential expression of the UCHL1 gene in lung adenocarcinoma and normal lung tissues, and the correlation between the UCHL1 gene and prognosis was also analyzed by the bioinformatics database TCGA. Meanwhile, we detected and analyzed the expression of UCHL1 and Ki-67 protein in a tissue microarray (TMA) containing 150 patients with lung adenocarcinoma by immunohistochemistry (IHC) and clinicopathological characteristics by TCGA database. In vitro experiments, we knocked down the UCHL1 gene of A549 cells and detected the changes in cell migration, invasion, and apoptosis. At the same time, we analyzed the effect of UCHL1 on anti-tumor drug sensitivity of lung adenocarcinoma by a bioinformatics database. In terms of the detection rate of lung adenocarcinoma indicators, we analyzed the impact of UCHL1 combined with common clinical indicators on the detection rate of lung adenocarcinoma through a bioinformatics database. Results In this study, the analysis of UCHL1 protein expression in lung adenocarcinoma proved that obviously higher UCHL1 protein level was discovered in lung adenocarcinoma tissues. The expression of UCHL1 was closely related to poor clinical outcomes. Interestingly, a significantly positive correlation between the expression of UCHL1 and Ki-67-indicated UCHL1 was associated with tumor migration and invasion. Through executing loss of function tests, we affirmed that silencing of UCHL1 expression significantly inhibited migration and invasion of lung adenocarcinoma cells in vitro. Furthermore, lung adenocarcinoma cells with silenced UCHL1 showed a higher probability of apoptosis. In terms of the detection rate of lung adenocarcinoma indicators, we discovered UCHL1 could improve the detection rate of clinical lung adenocarcinoma and affect drug sensitivity. Conclusion In lung adenocarcinoma, UCHL1 promotes tumor migration, invasion, and metastasis by inhibiting apoptosis and has an important impact on the clinical drug treatment of lung adenocarcinoma. In addition, UCHL1 can improve the detection rate of clinical lung adenocarcinoma. Above all, UCHL1 may be a new marker for the diagnosis of lung adenocarcinoma and provide a new target for the treatment of clinical diseases.

Abstract At present, the treatment of esophageal cancer (EC) is mainly surgical and drug treatment. However, due to drug resistance, these therapies can not effectively improve the prognosis of patients with the EC. Therefore, a multigene prognostic risk scoring system was constructed by bioinformatics analysis method to provide a theoretical basis for the prognosis and treatment decision of EC. The gene expression profiles and clinical data of esophageal cancer patients were gathered from the Cancer Genome Atlas TCGA database, and the differentially expressed genes (DEGs) were screened by R software. Genes with prognostic value were screened by Kaplan Meier analysis, followed by functional enrichment analysis. A cox regression model was used to construct the prognostic risk score model of DEGs. ROC curve and survival curve were utilized to evaluate the performance of the model. Univariate and multivariate Cox regression analysis was used to evaluate whether the model has an independent prognostic value. Network tool mirdip was used to find miRNAs that may regulate risk genes, and Cytoscape software was used to construct gene miRNA regulatory network. GSCA platform is used to analyze the relationship between gene expression and drug sensitivity. 41 DEGs related to prognosis were pre-liminarily screened by survival analysis. A prognostic risk scoring model composed of 8 DEGs (APOA2, COX6A2, CLCNKB, BHLHA15, HIST1H1E, FABP3, UBE2C and ERO1B) was built by Cox regression analysis. In this model, the prognosis of the high-risk score group was poor (P

Small satellites are efficient at performing Earth science from space due to their limited cost and size. Small satellites (cubesats) achieve much with limited power production/storage, heat dissipation, data storage, and ground contact points/bandwidth. As such it is beneficial to offload as much as possible to ground support systems. Consider the HyperAngular Rainbow Polarimeter (HARP) Cubesat. Its goals were to serve as a technical demonstration prior to the development of HARP2 aboard the NASA Plankton Aerosol Cloud and ocean Ecosystem (PACE) mission and to serve as an Earth viewing remote sensing platform which measured the characteristics of clouds and aerosols. HARP cubesat was limited to taking 5-minute capture sequences once every 24 h. It took approximately 10 such captures before it needed to perform data downlink and have its memory cleared for continued use. A ground station at NASA Wallops supported HARP with approximately three points of contact each day. To maximize the value of each capture, ground support software was developed leveraging public data to inform the schedule of each capture. In this paper, we review the algorithms and data sources that allowed us to: 1; predict the HARP orbital track a week in advance, 2; predict also the location of other remote sensing satellites and ground stations relative to HARP, 3; predict the ground view geometry of the instrument along its orbital track, 4; compare global climatological data products of clouds and aerosols along the predicted orbital tracks, and 5; identify and integrate important ground target locations based on remote sensing literature and ongoing natural phenomena. This HARP Orbital Prediction System (HOPS) made HARP into a successful technical demonstration which also offered significant science value. The HOPS system presents a valuable methodology for small satellites to operate efficiently despite their limited capabilities. HOPS is also a useful testbed for studying the sensitivity of scene geometry. Using HOPS, we show that for a wide field-of-view (FOV) instrument, like HARP, latitude/longitude geolocation varies by approximately 0.1+ at a height of 8-10 km. Scattering angles vary less than 0.01+ at similar heights, with the worst performance near direct backscatter (180+). [ABSTRACT FROM AUTHOR]

In order to improve the driving performance of four-wheel drive electric vehicles and realize precise control of their speed, a Chaotic Random Grey Wolf Optimization-based PID in-wheel motor control algorithm is proposed in this paper. Based on an analysis of the structural principles of electric vehicles, mathematical and simulation models for the whole vehicle are established. In order to improve the control performance of the hub motor, the traditional Grey Wolf Optimization algorithm is improved. In particular, an enhanced population initialization strategy integrating sine and cosine random distribution factors into a Kent chaotic map is proposed, the weight factor of the algorithm is improved using a sine-based non-linear decreasing strategy, and the population position is improved using the random proportional movement strategy. These strategies effectively enhance the global optimization ability, convergence speed, and optimization accuracy of the traditional Grey Wolf Optimization algorithm. On this basis, the CR-GWO-PID control algorithm is established. Then, the software and hardware of an in-wheel motor controller are designed and an in-wheel motor bench test system is built. The simulation and bench test results demonstrate the significantly improved response speed and control accuracy of the proposed in-wheel motor control system.

Sedimentary phosphorus is a crucial potential source of phosphorus in the eutrophic lake ecosystem. Different ecological types are supposed to affect the presence and variation of sediment phosphorus. On the basis of field investigations, the total sediment phosphorus load in Zhushan Bay was 1,457.48 mg/kg, nearly four times that of the hydrophyte-dominated area. Thereinto, 41.1% was in the form of iron and aluminum-bound phosphorus, which explicitly indicated the phosphorus contamination there. Analytical methods such as Pearson correlation, contamination assessment and principal component analysis were conducted to find out that ‘contamination’ was not equivalent to ‘release risk’. The contamination classification of East Lake Taihu was ‘clean’ in general. However, 63.3% of the total phosphorus could be mobilized under certain conditions. Therefore, light phosphorus loading does not equate to less release risk. In the long run, the implicit phosphorus release by the activation of organic phosphorus in hydrophytic areas needs close attention. This study provides a reference to understand the influence of hydrophytes and algae on the phosphorus cycle of sediment. HIGHLIGHTS Light phosphorus loading does not equate to less release risk.; Under anaerobic conditions, more than 50% of organic phosphorus could be activated.; In the long run, the phosphorus release potential of the hydrophytic bay needs close attention.; The negative effects of algae on sediment phosphorus mainly start since their decay.;

Abstract The monthly and hourly climatology of Saharan dust layer height over the Atlantic, at a spatial resolution of ∼10 km, is obtained for the first time, via a passive remote sensing technique. The technique is applied to multiple years of Earth Polychromatic Imaging Camera (EPIC) data collected at the Lagrange‐1 point, generating a climate data record (CDR) of aerosol optical centroid height (AOCH). This CDR offers unprecedented spatial coverage and diurnal sampling compared to spaceborne lidars (CALIOP and CATS). Our results show high correspondence with CALIOP data in domain‐averaged monthly variations and with CATS data in diurnal variations, respectively. A principal component analysis (PCA) reveals the dominant role of dust transport in regulating AOCH variation, whereas the impact of the boundary layer is less significant. MERRA‐2 and satellite retrievals respectively display zero and 200–1,000 m of diurnal variation of AOCH, highlighting the uniqueness of EPIC AOCH CDR in constraining climate models.

Background: Spontaneous perforation of pyometra is a rare clinical emergency with high mortality. As pyometra perforation is difficult to recognize pre-operatively, many cases are mis-diagnosed as gastrointestinal (GI) rupture. This study aimed to develop a strategy to improve diagnostic accuracy of spontaneous uterine perforation in female patients with acute abdomen. Methods: Twenty-two women with spontaneous rupture of the uterus (twenty cases previously reported in the literature plus two cases from the authors’ hospital) were included in the study group, another 22 menopausal patients with GI perforation were selected as the control group. Radiologists carefully reviewed the CT images and reports and summarized some common signs in patients with spontaneous perforation of pyometra. GI patients’ CT images were also scrutinized for these characteristic signs. The occurrence of these features was calculated in both groups. All patients underwent abdominal surgical exploration and most of patients diagnosed with spontaneous perforation of pyometra received hysterectomy and bilateral oophorectomy. Results: Five characteristics were specifically detected in patients with uterine spontaneous perforation: (1) Fluid collected in the cul-de-sac, incidence 95.5%; (2) Fluid in the uterine cavity, incidence 100%; (3) Intra-uterine free air, incidence 90.9%; (4) Free air around the uterus, incidence 77.2%; (5) Defects on the uterine wall, incidence 72.7%. However, these five signs were rarely observed in control patients with GI perforation. A dignostic strategy combined clinical findings with raidiological features were developed to help identify these patients. Conclusions: The above five CT characteristics and the developed dignostic algorithm could be used as a tool to facilitate the preoperative diagnosis of spontaneous perforation of pyometra, although more tests are needed in large samples of cases.

Functional devices in the THz band will provide a highly important technical guarantee for the promotion and application of 6G technology. We sought to design a high-performance sensor with a large area, high responsiveness, and low equivalent noise power, which is stable at room temperature for long periods and still usable under high humidity; it is suitable for the environment of marine remote sensing technology and has the potential for mass production. We prepared a Te film with high stability and studied its crystallization method by comparing the sensing and detection effects of THz waves at different annealing temperatures. It is proposed that the best crystallization and detection effect is achieved by annealing at 100 °C for 60 min, with a sensitivity of up to 19.8 A/W and an equivalent noise power (NEP) of 2.8 pW Hz−1/2. The effective detection area of the detector can reach the centimeter level, and this level is maintained for more than 2 months in a humid environment at 30 °C with 70–80% humidity and without encapsulation. Considering its advantages of stability, detection performance, large effective area, and easy mass preparation, our Te thin film is an ideal sensor for 6G ocean remote sensing technology.

This study focused on the association of dietary patterns and Tibetan featured foods with high-altitude polycythemia (HAPC) in Naqu, Tibet, to explore the risk factors of HAPC in Naqu, Tibet, to raise awareness of the disease among the population and provide evidence for the development of prevention and treatment interventions. A 1:2 individual-matched case-control study design was used to select residents of three villages in the Naqu region of Tibet as the study population. During the health examination and questionnaire survey conducted from December 2020 to December 2021, a sample of 1,171 cases was collected. And after inclusion and exclusion criteria and energy intake correction, 100 patients diagnosed with HAPC using the “Qinghai criteria” were identified as the case group, while 1,059 patients without HAPC or HAPC -related diseases were identified as the control group. Individuals were matched by a 1:2 propensity score matching according to gender, age, body mass index (BMI), length of residence, working altitude, smoking status, and alcohol status. Dietary patterns were determined by a principal component analysis, and the scores of study subjects for each dietary pattern were calculated. The effect of dietary pattern scores and mean daily intake (g/day) of foods in the Tibetan specialty diet on the prevalence of HAPC was analyzed using conditional logistic regression. After propensity score matching, we found three main dietary patterns among residents in Naqu through principal component analysis, which were a “high protein pattern,” “snack food pattern,” and “vegetarian food pattern.” All three dietary patterns showed a high linear association with HAPC (p < 0.05) and were risk factors for HAPC. In the analysis of the relationship between Tibetan featured foods and the prevalence of HAPC, the results of the multifactorial analysis following adjustment for other featured foods showed that there was a positive correlation between the average daily intake of tsampa and the presence of HAPC, which was a risk factor. Additionally, there was an inverse correlation between the average daily intake of ghee tea and the presence of HAPC, which was a protective factor.

BackgroundCervical cancer has become a worldwide concern owing to its high incidence and mortality rates. To date, high-altitude areas of Tibet have not benefited from any large-scale cervical cancer screening programs. Therefore, we initiated a screening program to investigate the prevalence of human papilloma virus (HPV) and HPV genotype distribution to reveal cervical cancer and its precursor which lead to morbidity among women in the city of Nagqu in northern Tib3et.MethodsA total of 25,173 women were recruited to undergo HPV genotype tests between June and December 2019. Women infected with HPV 16 and/or 18 underwent colposcopy and histological examination. Women with other high-risk HPV type (hr-HPV) underwent cytological tests to determine whether to conduct further colposcopy and histological examination for diagnosis. HPV prevalence was calculated in the total population and further stratified according to various parameters, such as age group, area location (altitude level), and single or mixed infection status. The HPV genotype distribution was also investigated accordingly. Cervical lesions revealed by further colposcopic findings were also analyzed; high-grade and malignant lesion morbidities were calculated in total and in each county. Most data were collected and analyzed using descriptive and consistency check statistical methods, and a risk factor investigation for HPV infection was performed using logistic regression models.ResultsThe total HPV infection rate among women in Nagqu was 13.42%. Of the 25,173 women in the study, 999 (3.97%) were HPV 16/18 positive, 2,379 (9.45%) were other hr-HPV-positive, and 21,795 (86.58%) were HPV-negative. The five most common HPV genotypes, accounting for more than 60% of all HPV infections in Nagqu people, were HPV 16, 58, 31, 18, and 52. Tibetan women younger than 20 years and older than 60 years were the two age groups with the highest rates of HPV infection, 26.7% and 19.8%, respectively. Among the HPV-positive women, 2,656 (78.33%) were infected with a single strain and 732 (21.67%) were infected with multiple strains (more than two genotypes). HPV prevalence increased in high-altitude areas (positive rate highest in Nyima with an altitude of 5,000 m, 23.9%) and decreased in relatively low-altitude areas (positive rate lowest in Lhari with an altitude of 4,000 m, 6.6%). Multiple analyses showed that age, parity, age at first delivery, and altitude of residence were independent factors facilitating HPV infection in Tibetan women. High-grade and malignant cervical lesions revealed by histological findings were different among living locations, with the highest rates in Xainza, Baingoin, and Nyainrong, these being 2.019%, 1.820%, and 1.116%, respectively, among women in these areas.ConclusionOur survey provides an overall perspective on HPV genotype infection and cervical lesions in women in northern Tibet. The data not only provide useful information for the treatment of cervical lesions but also has great value in terms of the primary and secondary prevention measures that can be taken for women living in these regions.Clinical Trial Registrationwww.chictr.org.cn, indentifier ChiCTR2000035061.

Abstract The pathophysiology of coronavirus disease 19 (COVID-19) involves a multitude of host responses, yet how they unfold during the course of disease progression remains unclear. Here, through integrative analysis of clinical laboratory tests, targeted proteomes, and transcriptomes of 963 patients in Shanghai, we delineate the dynamics of multiple circulatory factors within the first 30 days post-illness onset and during convalescence. We show that hypercortisolemia represents one of the probable causes of acute lymphocytopenia at the onset of severe/critical conditions. Comparison of the transcriptomes of the bronchoalveolar microenvironment and peripheral blood indicates alveolar macrophages, alveolar epithelial cells, and monocytes in lungs as the potential main sources of elevated cytokines mediating systemic immune responses and organ damages. In addition, the transcriptomes of patient blood cells are characterized by distinct gene regulatory networks and alternative splicing events. Our study provides a panorama of the host responses in COVID-19, which may serve as the basis for developing further diagnostics and therapy.

Abstract Despite the significant advances in the treatment of multiple myeloma (MM), this disease is still considered incurable because of relapse and chemotherapy resistance, underscoring the need to seek novel therapies with different mechanisms. Anlotinib, a novel multi-targeted tyrosine kinase inhibitor (TKI), has exhibited encouraging antitumor activity in several preclinical and clinical trials, but its effect on MM has not been studied yet. In this study, we found that anlotinib exhibits encouraging cytotoxicity in MM cells, overcomes the protective effect of the bone marrow microenvironment and suppresses tumor growth in the MM mouse xenograft model. We further examined the underlying molecular mechanism and found that anlotinib provokes cell cycle arrest, induces apoptosis and inhibits multiple signaling pathways. Importantly, we identify c-Myc as a novel direct target of anlotinib. The enhanced ubiquitin proteasomal degradation of c-Myc contributes to the cell apoptosis induced by anlotinib. In addition, anlotinib also displays strong cytotoxicity against bortezomib-resistant MM cells. Our study demonstrates the extraordinary anti-MM effect of anlotinib both in vitro and in vivo, which provides solid evidence and a promising rationale for future clinical application of anlotinib in the treatment of human MM.

Abstract Background DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach. Methods The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear mixed models adjusting for age, sex, smoking, and study-specific and technical variables. Summary results were meta-analyzed within and across ethnicities. Findings were assessed using integrative epigenomics methods and pathway analyses. Results We identified 93 DMPs associated with eGFR at an FDR of 0.05 and replicated 13 and 1 DMPs across independent samples in trans-ethnic and African American meta-analyses, respectively. The study also validated 6 previously published DMPs. Identified DMPs showed significant overlap enrichment with DNase I hypersensitive sites in kidney tissue, sites associated with the expression of proximal genes, and transcription factor motifs and pathways associated with kidney tissue and kidney development. Conclusions We uncovered trans-ethnic and ethnic-specific DMPs associated with eGFR, including DMPs enriched in regulatory elements in kidney tissue and pathways related to kidney development. These findings shed light on epigenetic mechanisms associated with kidney function, bridging the gap between population-specific eGFR-associated DNAm and tissue-specific regulatory context.

To better understand its mechanism of activity towards higher alcohols, we overexpressed and purified new Geotrichum candidum GDH (GcGDH). The purified GcGDH (50.27 kDa) was then crystallized, and the crystal diffracted to a resolution of 2.3 Å using X-ray diffraction. We found that the GcGDH crystal structure belonged to space group P212121 and was comprised of two hexamers organized into an asymmetric unit, with each subunit consisting of 452 amino acid residues. The binding sites between higher alcohols or L-glutamic acid and GcGDH were consistent. The optimal reaction conditions for GcGDH and hexanol were a pH of 4.0 and temperature of 30 °C, and those for GcGDH and monosodium glutamate (MSG) were a pH of 8.0 and temperature of 20 °C. The Km values for hexanol and MSG were found to be 74.78 mM and 0.018 mM, respectively. Mutating GcGDH Lys 113 to either Ala or Gly caused a dramatic reduction in its catalytic efficiency towards both MSG and hexanol, suggesting that Lys 113 is essential to the active site of GcGDH.

Abstract Carbonaceous materials are considered strong candidates as anode materials for sodium‐ion batteries (SIBs), which are expected to play an indispensable role in the carbon‐neutral era. Herein, novel braided porous carbon fibres (BPCFs) are prepared using the chemical vapour deposition (CVD) method. The BPCFs possess interwoven porous structures and abundant vacancies. The growth mechanism of the BPCFs can be attributed to the polycrystalline transformation of the nanoporous copper catalyst in the early stage of CVD process. Density functional theory calculations suggest that the Na+ adsorption energies of the mono‐vacancy edges of the BPCFs (−1.22 and −1.09 eV) are lower than that of an ideal graphene layer (−0.68 eV), clarifying in detail the adsorption‐dominated sodium storage mechanism. Hence, the BPCFs as an anode material present an outstanding discharge capacity of 401 mAh g−1 at 0.1 A g−1 after 500 cycles. Remarkably, this BPCFs anode, under high‐mass‐loading of 5 mg cm−2, shows excellent long‐term cycling ability with a reversible capacity of 201 mAh g−1 at 10 A g−1 over 1000 cycles. This study provided a novel strategy for the development of high‐performance carbonaceous materials for SIBs.

Social impact bonds (SIBs) have emerged as an innovative financial instrument designed to support the social service sector in delivering innovative social programs. In particular, SIBs can be used to finance prevention of homelessness among those regarded as vulnerable. There is little evidence that outcomes from SIB-funded programs are significantly different compared to more traditional programs. This is the first scoping review of academic and gray literature that explores the main features and outcomes from all SIBs for homelessness based on evidence, addressing an important gap in the literature. The scoping review provides a transparent and comprehensive approach for mapping areas of this research. A total of 73 studies and articles were found eligible for inclusion. These concerned 32 SIBs for homelessness implemented in the United Kingdom, the United States, Australia, and Belgium. The review found that academic papers on SIBs for homelessness lack evidence-based analysis, while gray literature lacks transparency, especially in evaluation method and outcome. We found that fourteen projects met their target outcomes. The common features of these SIBs were a navigator intervention model, effective partnership working, and use of Special Purpose Vehicles. Our findings show that it is necessary for the managers of SIBs to improve outcome metrics and evaluation methods, support target groups fairly, and attract more private investors to finance SIBs for better addressing homelessness.

Satellite retrievals of columnar nitrogen dioxide (NO2) are essential for the characterization of nitrogen oxides (NOx) processes and impacts. The requirements of modeled a priori profiles present an outstanding bottleneck in operational satellite NO2 retrievals. In this work, we instead use neural network (NN) models trained from over 360,000 radiative transfer (RT) simulations to translate satellite radiances across 390-495 nm to total NO2 vertical column (NO2C). Despite the wide variability of the many input parameters in the RT simulations, only a small number of key variables were found essential to the accurate prediction of NO2C, including observing angles, surface reflectivity and altitude, and several key principal component scores of the radiances. In addition to the NO2C, the NN training and cross-validation experiments show that the wider retrieval window allows some information about the vertical distribution to be retrieved (e.g., extending the rightmost wavelength from 465 to 495 nm decreases the root-mean-square-error by 0.75%) under high-NO2C conditions. Applying to four months of TROPOMI data, the trained NN model shows strong ability to reproduce the NO2C observed by the ground-based Pandonia Global Network. The coefficient of determination (R2, 0.75) and normalized mean bias (NMB, -33%) are competitive with the level 2 operational TROPOMI product (R2=0.77, NMB=−29%) over clear (geometric cloud fraction

Remote sensing measurements from multi-angle polarimeters (MAPs) contain rich aerosol microphysical property information, and these sensors have been used to perform retrievals in optically complex atmosphere and ocean systems. Previous studies have concluded that, generally, five moderately separated viewing angles in each spectral band provide sufficient accuracy for aerosol property retrievals, with performance gradually saturating as angles are added above that threshold. The Hyper-Angular Rainbow Polarimeter (HARP) instruments provide high angular sampling with a total of 90–120 unique angles across four bands, a capability developed mainly for liquid cloud retrievals. In practice, not all view angles are optimal for aerosol retrievals due to impacts of clouds, sunglint, and other impediments. The many viewing angles of HARP can provide resilience to these effects, if the impacted views are screened from the dataset, as the remaining views may be sufficient for successful analysis. In this study, we discuss how the number of available viewing angles impacts aerosol and ocean color retrieval uncertainties, as applied to two versions of the HARP instrument. AirHARP is an airborne prototype that was deployed in the ACEPOL field campaign, while HARP2 is an instrument in development for the upcoming NASA Plankton, Aerosol, Cloud, ocean Ecosystem (PACE) mission. Based on synthetic data, we find that a total of 20–30 angles across all bands (i.e., five to eight viewing angles per band) are sufficient to achieve good retrieval performance. Following from this result, we develop an adaptive multi-angle polarimetric data screening (MAPDS) approach to evaluate data quality by comparing measurements with their best-fitted forward model. The FastMAPOL retrieval algorithm is used to retrieve scene geophysical values, by matching an efficient, deep learning-based, radiative transfer emulator to observations. The data screening method effectively identifies and removes viewing angles affected by thin cirrus clouds and other anomalies, improving retrieval performance. This was tested with AirHARP data, and we found agreement with the High Spectral Resolution Lidar-2 (HSRL-2) aerosol data. The data screening approach can be applied to modern satellite remote sensing missions, such as PACE, where a large amount of multi-angle, hyperspectral, polarimetric measurements will be collected.

Dietary pattern is quite distinct among the inhabitants of high-altitude areas because of environmental and geographical uniqueness; hence, it is important to investigate this data as accurately as possible. However, very few data are related to these populations up to now. Based on the food frequency questionnaire (FFQ) used in the Chinese population, a revised Tibetan edition was developed with respect to the lifestyle in high-altitude areas. After assessment of validity and reproducibility, a nutrition intake survey was conducted among 1,071 randomly sampled Tibetan people. In addition, the Bland–Altman approach was used to compare the agreement between the two dietary tools. For the reproducibility analysis, intraclass correlation coefficients (ICC) were calculated to examine the agreement of food groups and nutrients from the two FFQs (FFQ1 and FFQ2). Nutrient intake was calculated using food composition tables. For the validity analysis, Pearson's correlation of food groups intakes varied from 0.22 to 0.91 (unadjusted). The correlations of nutrients ranged from 0.24 to 0.76 (unadjusted). In the analysis of reliability, the ICC of food groups varied from 0.27 to 0.70 (unadjusted). The ICC of nutrient intakes ranged from 0.22 to 0.87 (unadjusted). The results of nutritional analysis showed that ~25% of foods consumed frequently were traditional Tibetan foods. However, traditional Han foods were frequently consumed. In addition, the energy, iron, and protein intakes for male or female subjects were close to the Chinese Dietary Nutrient Reference Intake (Chinese DRIs); however, fat and sodium intakes were significantly higher than the Chinese DRIs. Interestingly, lower intakes of other types of nutrition, such as vitamin C were detected in people living in high-altitude areas. Our data indicated that excess consumption of fat and sodium and insufficient intake of vitamin C were common among Tibetan people, as compared with the most Chinese people living in the plateau areas. More investigations are needed to reveal the association between the food intake style and high-altitude endemic diseases.

A series of huge smoke plume events from the largest wildfire season recorded in California’s modern history has occurred in 2020. Here, a research algorithm was modified to retrieve the aerosol optical centroid height (AOCH) and aerosol optical depth (AOD) from Earth Polychromatic Imaging Camera (EPIC) measurements. The research focus is to gain insights of the algorithm’s feasibility in heavy smoke conditions to study the diurnal variation of AOCH; this is only made possible via EPIC due to its unique position at Lagrange-1 point and its equipment of O2 B-band at which the vegetated surface reflectance is low. Vicarious calibration is applied to the EPIC 443, 680 and 688 nm channels based on the Tropospheric Monitoring Instrument (TROPOMI) observation. This new calibration leads to a better agreement of AOCH values between EPIC retrievals and the counterparts derived from the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) aerosol extinction vertical profile. The hourly variation of AOCH up to 0.45 km on September 7 is shown to have important implications for estimating hourly change of surface PM2.5, although more quantitative studies are needed in the future.

Abstract Background Alternaria sp. MG1, an endophytic fungus isolated from grape, is a native producer of resveratrol, which has important application potential. However, the metabolic characteristics and physiological behavior of MG1 still remains mostly unraveled. In addition, the resveratrol production of the strain is low. Thus, the whole-genome sequencing is highly required for elucidating the resveratrol biosynthesis pathway. Furthermore, the metabolic network model of MG1 was constructed to provide a computational guided approach for improving the yield of resveratrol. Results Firstly, a draft genomic sequence of MG1 was generated with a size of 34.7 Mbp and a GC content of 50.96%. Genome annotation indicated that MG1 possessed complete biosynthesis pathways for stilbenoids, flavonoids, and lignins. Eight secondary metabolites involved in these pathways were detected by GC–MS analysis, confirming the metabolic diversity of MG1. Furthermore, the first genome-scale metabolic network of Alternaria sp. MG1 (named iYL1539) was reconstructed, accounting for 1539 genes, 2231 metabolites, and 2255 reactions. The model was validated qualitatively and quantitatively by comparing the in silico simulation with experimental data, and the results showed a high consistency. In iYL1539, 56 genes were identified as growth essential in rich medium. According to constraint-based analysis, the importance of cofactors for the resveratrol biosynthesis was successfully demonstrated. Ethanol addition was predicted in silico to be an effective method to improve resveratrol production by strengthening acetyl-CoA synthesis and pentose phosphate pathway, and was verified experimentally with a 26.31% increase of resveratrol. Finally, 6 genes were identified as potential targets for resveratrol over-production by the recently developed methodology. The target-genes were validated using salicylic acid as elicitor, leading to an increase of resveratrol yield by 33.32% and the expression of gene 4CL and CHS by 1.8- and 1.6-fold, respectively. Conclusions This study details the diverse capability and key genes of Alternaria sp. MG1 to produce multiple secondary metabolites. The first model of the species Alternaria was constructed, providing an overall understanding of the physiological behavior and metabolic characteristics of MG1. The model is a highly useful tool for enhancing productivity by rational design of the metabolic pathway for resveratrol and other secondary metabolites.