DRdriver: identifying drug resistance driver genes using individual-specific gene regulatory network.

Drug resistance is one of principal limiting factors for cancer treatment. Several mechanisms, especially mutation, have been validated to implicate in drug resistance. In addition, drug resistance is heterogeneous, which makes an urgent need to explore the personalized driver genes of drug resistance. Here, we proposed an approach DRdriver to identify drug resistance driver genes in individual-specific network of resistant patients. First, we identified the differential mutations for each resistant patient. Next, the individual-specific network, which included the genes with differential mutations and their targets, was constructed. Then, the genetic algorithm was utilized to identify the drug resistance driver genes, which regulated the most differentially expressed genes and the least non-differentially expressed genes. In total, we identified 1202 drug resistance driver genes for 8 cancer types and 10 drugs. We also demonstrated that the identified driver genes were mutated more frequently than other genes and tended to be associated with the development of cancer and drug resistance. Based on the mutational signatures of all driver genes and enriched pathways of driver genes in brain lower grade glioma treated by temozolomide, the drug resistance subtypes were identified. Additionally, the subtypes showed great diversity in epithelial-mesenchyme transition, DNA damage repair and tumor mutation burden. In summary, this study developed a method DRdriver for identifying personalized drug resistance driver genes, which provides a framework for unlocking the molecular mechanism and heterogeneity of drug resistance.

Co-expression network analysis of diverse wheat landraces reveals markers of early thermotolerance and a candidate master regulator of thermotolerance genes.

Triticum aestivum L. (bread wheat) is a crop relied upon by billions of people around the world, as a major source of both income and calories. Rising global temperatures, however, pose a genuine threat to the livelihood of these people, as wheat growth and yields are extremely vulnerable to damage by heat stress. Here we present the YoGI wheat landrace panel, comprising 342 accessions that show remarkable phenotypic and genetic diversity thanks to their adaptation to different climates. We quantified the abundance of 110 790 transcripts from the panel and used these data to conduct weighted co-expression network analysis and to identify hub genes in modules associated with abiotic stress tolerance. We found that the expression of three hub genes, all heat-shock proteins (HSPs), were significantly correlated with early thermotolerance in a validation panel of landraces. These hub genes belong to the same module, with one (TraesCS4D01G207500.1) being a candidate master-regulator potentially controlling the expression of the other two hub genes, as well as a suite of other HSPs and heat-stress transcription factors (HSFs). In this work, therefore, we identify three validated hub genes, the expression of which can serve as markers of thermotolerance during early development, and suggest that TraesCS4D01G207500.1 is a potential master regulator of HSP and HSF expression - presenting the YoGI landrace panel as an invaluable tool for breeders wishing to determine and introduce novel alleles into modern varieties, for the production of climate-resilient crops.

Genomics of predictive radiation mutagenesis in oilseed rape: modifying seed oil composition.

Rapeseed is a crop of global importance but there is a need to broaden the genetic diversity available to address breeding objectives. Radiation mutagenesis, supported by genomics, has the potential to supersede genome editing for both gene knockout and copy number increase, but detailed knowledge of the molecular outcomes of radiation treatment is lacking. To address this, we produced a genome re-sequenced panel of 1133 M2 generation rapeseed plants and analysed large-scale deletions, single nucleotide variants and small insertion-deletion variants affecting gene open reading frames. We show that high radiation doses (2000 Gy) are tolerated, gamma radiation and fast neutron radiation have similar impacts and that segments deleted from the genomes of some plants are inherited as additional copies by their siblings, enabling gene dosage decrease. Of relevance for species with larger genomes, we showed that these large-scale impacts can also be detected using transcriptome re-sequencing. To test the utility of the approach for predictive alteration of oil fatty acid composition, we produced lines with both decreased and increased copy numbers of Bna.FAE1 and confirmed the anticipated impacts on erucic acid content. We detected and tested a 21-base deletion expected to abolish function of Bna.FAD2.A5, for which we confirmed the predicted reduction in seed oil polyunsaturated fatty acid content. Our improved understanding of the molecular effects of radiation mutagenesis will underpin genomics-led approaches to more efficient introduction of novel genetic variation into the breeding of this crop and provides an exemplar for the predictive improvement of other crops.

Legume nodulation and nitrogen fixation require interaction of DnaJ-like protein and lipid transfer protein.

The lipid transport protein (LTP) product of the AsE246 gene of Chinese milk vetch (Astragalus sinicus) contributes to the transport of plant-synthesized lipids to the symbiosome membranes (SMs) that are required for nodule organogenesis in this legume. However, the mechanisms used by nodule-specific LTPs remain unknown. In this study, a functional protein in the DnaJ-like family, designated AsDJL1, was identified and shown to interact with AsE246. Immunofluorescence showed that AsDJL1 was expressed in infection threads (ITs) and in nodule cells and that it co-localized with rhizobium, and an immunoelectron microscopy assay localized the protein to SMs. Via co-transformation into Nicotiana benthamiana cells, AsDJL1 and AsE246 displayed subcellular co-localization in the cells of this heterologous host. Co-immunoprecipitation assays confirmed that AsDJL1 interacted with AsE246 in nodules. The essential interacting region of AsDJL1 was determined to be the zinc finger domain at its C-terminus. Chinese milk vetch plants transfected with AsDJL1-RNAi had significantly decreased numbers of ITs, nodule primordia and nodules as well as reduced (by 83%) nodule nitrogenase activity compared with the controls. By contrast, AsDJL1 overexpression led to increased nodule fresh weight and nitrogenase activity. RNAi-AsDJL1 also significantly affected the abundance of lipids, especially digalactosyldiacylglycerol, in early-infected roots and transgenic nodules. Taken together, the results of this study provide insights into the symbiotic functions of AsDJL1, which may participate in lipid transport to SMs and play an essential role in rhizobial infection and nodule organogenesis.

Bismuth-doped fiber amplifier based on a linear cavity double pass structure operating in the O + E band.

Finding suitable fiber amplifiers is one of the key strategies to increase the transmission capacity of fiber links. Recently, bismuth-doped fiber amplifiers (BDFAs) have attracted much attention due to their distinctive ultra-wideband luminescence properties. In this paper, we propose a linear cavity double pass structure for BDFA operating in the O and E bands. The design creates a linear cavity within the amplifier by combining a fiber Bragg grating (FBG) and a fiber mirror to achieve dual-wavelength pump at 1240 nm and 1310 nm. Meanwhile, the configuration of a circulator and mirror facilitates bidirectional signal propagation through the BDFA, resulting in a double-pass amplification structure. We have tested and analyzed the performance of the linear cavity double pass structure BDFA under different pump schemes and compared it with the conventional structure BDFA. The results show that the gain spectrum of the new structure is shifted toward longer wavelengths, and the gain band is extended from the O band to the O and E bands compared with the conventional structure. In particular, the linear cavity double pass structure BDFA has more relaxed requirements on the stability of the pump and signal power. This work provides a positive reference for the design, application, and development of BDFAs.

Elevated first-trimester neutrophil elastase and proteinase 3 increase the risk of gestational diabetes mellitus and adverse fetal outcomes.

BACKGROUND: Chronic inflammation plays a vital role in the development of gestational diabetes mellitus (GDM). Studies in mouse models show that neutrophil serine proteases (NSPs), neutrophil elastase (NE) and proteinase-3 (PR3) are important drivers of chronic inflammation with consequent metabolic disturbances. This study evaluated the association of NE and PR3 with GDM development and adverse fetal outcomes. METHOD(S): This was a prospective cohort study. Serum PR3 and NE concentration was measured in all enrolled pregnant women in the first and the second trimester to determine the connection between NSPs and GDM and adverse fetal outcomes. Logistic regression, spline regression and linear regression analyses were applied to investigate the association of NE or PR3 with GDM development and adverse fetal outcomes. The concentration of NE and PR3 in placental biopsies was evaluated by semi-quantitative analysis of immunohistochemistry staining. RESULT(S): NE or PR3 concentration in the first trimester, rather than the second, increased more significantly in women with GDM than in those without, regardless of pre-pregnancy body mass index and age. There was a stepwise increase in GDM occurrence as well as comprehensive adverse fetal outcomes across tertiles of NE and PR3. NE and PR3 were positively associated with neutrophil count, pre-pregnancy BMI, plasma glucose level and newborn weight. Logistic regression revealed NE or PR3 to be independent risk factors for the development of GDM and comprehensive adverse fetal outcomes. Spline regression showed a significant increased risk of GDM occurrence and comprehensive adverse fetal outcomes when serum NE concentration exceeded 417.60 ng/mL and a similar result for PR3 and GDM occurrence when the latter exceeded 88.52 ng/mL. Immunohistochemistry data confirmed that enriched NE and PR3 content in placental tissue may have contributed to the development of GDM. CONCLUSION(S): This work demonstrates that excessive first-trimester NE and PR3 increase the risk of GDM development and comprehensive adverse fetal outcomes.

Retrospective cohort evaluation of non-HIV Castleman disease from a single academic center in Beijing, China.

The purpose is to ascertain the clinical impact of Castleman disease (CD) by reassessment of the real-world data from Peking University First Hospital (PKUFH). The results will contribute to the standardization of diagnosis and treatment on CDs. Based on the last 15-year retrospective real-world data from Peking University First Hospital (PKUFH), we reclassified and re-evaluated the clinical and pathological information of patients with pathologically suspected diagnosis of CD. A total of 203 patients were included in our study, in which the diagnosis of CD was confirmed in 189 cases, including 118 patients with unicentric CD (UCD, n = 118, 62.4%) and 71 patients with multicentric CD (MCD, n = 71, 37.6%). A total of 44.1% (n = 52) of UCDs in our cohort were complicated with paraneoplastic pemphigus (PNP). The treatment of UCD is primarily surgical, with a 5-year overall survival (OS) of 88.1%. Patients with PNP had a poorer prognosis than those without PNP (82.9% (95% CI 123-178) vs 92.8% (95% CI 168-196), log-rank p = 0.041). The rate of concurrent systemic symptoms was 74.6% (n = 53), and renal involvement occurred in 49.3% (n = 35) MCD patients. The MCD treatments were mainly chemotherapy regimens, with a 5-year OS of 77.6% (95% CI, 143-213). Patients with UCD demonstrate a better overall prognosis than patients with MCD. But the prognosis of those complicated with PNP was poor. The differential diagnosis of MCD is extensive. MCD treatment in China is heterogeneous. The inaccessibility of anti-IL-6-targeted drugs in China may contribute to the poor prognosis for patients with MCD.A preprint has previously been published (Guo et al. 34).

Development of a novel dynamic nosocomial infection risk management method for COVID-19 in outpatient settings.

BACKGROUND: Application of accumulated experience and management measures in the prevention and control of coronavirus disease 2019 (COVID-19) has generally depended on the subjective judgment of epidemic intensity, with the quality of prevention and control management being uneven. The present study was designed to develop a novel risk management system for COVID-19 infection in outpatients, with the ability to provide accurate and hierarchical control based on estimated risk of infection. METHODS: Infection risk was estimated using an auto regressive integrated moving average model (ARIMA). Weekly surveillance data on influenza-like-illness (ILI) among outpatients at Xuanwu Hospital Capital Medical University and Baidu search data downloaded from the Baidu Index in 2021 and 22 were used to fit the ARIMA model. The ability of this model to estimate infection risk was evaluated by determining the mean absolute percentage error (MAPE), with a Delphi process used to build consensus on hierarchical infection control measures. COVID-19 control measures were selected by reviewing published regulations, papers and guidelines. Recommendations for surface sterilization and personal protection were determined for low and high risk periods, with these recommendations implemented based on predicted results. RESULTS: The ARIMA model produced exact estimates for both the ILI and search engine data. The MAPEs of 20-week rolling forecasts for these datasets were 13.65% and 8.04%, respectively. Based on these two risk levels, the hierarchical infection prevention methods provided guidelines for personal protection and disinfection. Criteria were also established for upgrading or downgrading infection prevention strategies based on ARIMA results. CONCLUSION: These innovative methods, along with the ARIMA model, showed efficient infection protection for healthcare workers in close contact with COVID-19 infected patients, saving nearly 41% of the cost of maintaining high-level infection prevention measures and enhancing control of respiratory infections.

One-step sintering construction of electromagnetic synergistic Co7Fe3/Co@CBC nanocomposites for enhanced microwave absorption properties.

Based on the synergistic modulation of electromagnetic parameters and microstructure design, multidimensional porous magnetic carbon-based nanocomposites have become ideal materials with efficient absorption properties. What's more, a carbon-magnetic alloy composite is a commonly used and efficient microwave absorber. In this paper, Co7Fe3/Co@CBC (CFCC) nanocomposites with strong magnetism, a three-phase composition, and a three-dimensional porous structure were synthesized by reducing Fe2+ and Co2+ using chestnut-shell biomass carbon (CBC). Biomass carbon with a higher specific surface area provides numerous active sites for Co7Fe3 nanosheets and Co nanospheres to form three-dimensional ping-pong chrysanthemum-like nanocomposites, which generate rich heterogeneous interfaces and conductive network structures. By adjusting the amount of added biomass, the electromagnetic parameters can be effectively regulated to achieve efficient microwave absorption properties. When the amount of biomass added varies within the range of 1.0 to 2.5 g, all samples exhibit a favorable effective absorption bandwidth (EAB) of over 5.88 GHz. In particular, the CFCC-2.0 composite exhibits optimal microwave absorption properties, with a minimum reflection loss (RLmin) value of -59.25 dB and an EAB of 6.34 GHz at a thickness of 2.8 mm. The simulation and modeling analysis results of radar cross section (RCS) further confirm the exceptional attenuation capability of composite materials at multiple incident angles. The exceptional microwave absorption properties and stability of EAB for the Co7Fe3/Co@CBC nanocomposite make it a promising candidate in the field of absorbing materials. This work also provides some feasible ideas for designing stable broadband wave-absorbing materials.

A taste alteration-related scale assesses megestrol to improve chemotherapy-induced anorexia.

PURPOSE: We evaluated the efficacy of megestrol in improving chemotherapy-related anorexia by analyzing the related scales of taste alteration. METHODS: We conducted the current study on a group of advanced patients with cancer with two or more chemotherapy cycles. The chemotherapy-induced taste alteration scale (CiTAs) scale helped assess the megestrol effects on basic taste perception, aversive taste changes, unpleasant symptoms, and associated concerns. Furthermore, the Short Nutritional Assessment Questionnaire scale (SNAQ) helped measure the impact of megestrol on malnutrition likelihood in patients experiencing chemotherapy-induced anorexia. The World Health Organization Quality of Life (WHOQOL)-BREF Scale was used to evaluate the quality of life of participants, producing scores related to physical health, psychological well-being, environmental factors, and social relationships. RESULTS: The CiTAs scale assessment indicated that administering megestrol significantly enhanced taste perception among advanced patients with cancer undergoing chemotherapy. Notably, the megestrol group patients showed significantly higher Short Nutritional Assessment Questionnaire (SNAQ) scores than the control group. The megestrol group patients also exhibited higher physiological (PHYS) scores than their control group counterparts. However, this distinction was not statistically significant. The study findings indicate that patients who received megestrol demonstrated significantly higher scores in psychological (PSYCH) and environmental(ENVIR) domains than the control group. Furthermore, megestrol administration was associated with significantly elevated SOCIL and ENVIR levels in patients. CONCLUSION: The proficient efficacy evaluation of megestrol in enhancing appetite, mitigating malnutrition likelihood, and improving the quality of life of chemotherapy-induced anorexic patients can be achieved through taste-related scales.

Association between serum 25-hydroxyvitamin D and vitamin D dietary supplementation and risk of all-cause and cardiovascular mortality among adults with hypertension.

BACKGROUND: The relationship between vitamin D status and mortality among adults with hypertension remains unclear. METHODS: This prospective cohort study involved a sample of 19,500 adults with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018. We utilized a weighted COX proportional hazard model to assess the association between vitamin D status and mortality. This statistical model calculates hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI). RESULTS: The study indicated that lower serum 25(OH)D concentration was associated with an increased risk of all-cause mortality among individuals with hypertension. Specially. Those with concentrations between 25.0 and 49.9 nmol/L (HR = 1.71, 95%CI = 1.22-2.40) and less than 25.0 nmol/L (HR = 1.97, 95%CI = 1.15-3.39) had higher hazard ratios for all-cause mortality. Individuals with hypertension who took vitamin D supplements had a lower risk of all-cause mortality, but not the risk of CVD mortality (HR 0.75, 95%CI 0.54-1.03), compared to those who did not supplement (HR = 0.76, 95%CI = 0.61-0.94). Subgroup analysis further revealed that vitamin D supplementation was associated with a reduced risk of all-cause mortality among individuals without diabetes (HR = 0.65, 95%CI = 0.52-0.81) and individuals without CVD (HR = 0.75, 95%CI = 0.58-0.97), and a decreased risk of CVD mortality among individuals without diabetes (HR = 0.63, 95%CI = 0.45-0.88) and without CVD (HR = 0.61, 95%CI = 0.40-0.92). Furthermore, higher-dose vitamin D supplementation was also associated with a greater reduction in all-cause mortality among hypertensive individuals, and there was the potential synergistic effect of combining normal-dose calcium and vitamin D supplementation, showing a superior effect on mortality compared to low-dose supplementation in adults with hypertension. CONCLUSIONS: This prospective cohort study demonstrated a significant association between lower serum 25 (OH)D concentration and increased all-cause mortality among adults with hypertension. Furthermore, the study found that vitamin D supplementation had a strong and significantly positive correlation with reduced all-cause and CVD mortality among hypertensive individuals without diabetes or CVD. This positive correlation suggests that vitamin D supplementation could potentially be an effective strategy to reduce the risk of mortality in this specific group of people.

Doxorubicin-loaded PEG-CdTe QDs conjugated with anti-CXCR4 mAbs: a novel delivery system for extramedullary multiple myeloma treatment.

Extramedullary multiple myeloma (EMM) is defined as the presence of plasma cells outside the bone marrow of multiple myeloma patients, and its prognosis is poor. High-dose chemotherapy with autologous stem cell transplantation, as a good option on early lines of therapy, has retained the survival benefit of youny EMM patients, but is intolerant for the majority of old patients because of drug cytotoxicity. To essentially address the intolerance above, we designed a CXCR4-PEG-CdTe-DOX (where CXCR4: chemokine receptor 4; PEG-CdTe: polyethylene glycol-modified cadmium telluride; DOX:doxorubicin) nanoplatform. First, CXCR4 is highly expressed in extramedullary plasma cells. Second, PEG-CdTe a drug carrier that controls drug release, can reduce adverse reactions, prolong drug (e.g, DOX) circulation time in the body, and form a targeting carrier after connecting antibodies. In vitro experiments showed CXCR4-PEG-CdTe-DOX facilitated intracellular drug accumulation through active CXCR4 targeting and released DOX into the microenvironment in a pH-controlled manner, enhancing the therapeutic efficacy and apoptosis rate of myeloma cells (U266). Therefore, targeted chemotherapy mediated by CXCR4-PEG-CdTe-DOX is a promising option for EMM treatment.

Lanthanum interferes with the fundamental rhythms of stomatal opening, expression of related genes, and evapotranspiration in Arabidopsis thaliana.

The accumulation of rare earth elements (REEs) in the global environment poses a threat to plant health and ecosystem stability. Stomata located on leaves serve as the primary site for plant responses to REE-related threats. This study focused on lanthanum [La(III)], a prevalent REE in the atmospheric environment. Using interdisciplinary techniques, it was found that La(III) (≤80 µM) interfered with the fundamental rhythms of stomatal opening, related gene expression, and evapotranspiration in plants. Specifically, when exposed to low concentrations of La(III) (15 and 30 µM), the expression levels of six genes were increased, stomatal opening was enhanced, and the evapotranspiration rate was accelerated. The interference on stomatal rhythms was enhanced with higher concentrations of La(III) (60 and 80 µM), increasing the expression levels of six genes, stomatal opening, and evapotranspiration rate. To counter the interference of low concentrations of La(III) (15 and 30 µM), plants accelerated nutrient replenishment through La(III)-induced endocytosis, which the redundant nutrients enhanced photosynthesis. However, replenished nutrients failed to counter the disruption of plant biological rhythms at higher concentrations of La(III) (60 and 80 µM), thus inhibiting photosynthesis due to nutrient deficit. The interference of La(III) on these biological rhythms negatively affected plant health and ecosystem stability.

Quercetin nanocrystals prepared using a microfluidic chip with improved in vitro dissolution.

OBJECTIVE: In order to improve the dissolution property of quercetin (QCT), the quercetin nanocrystals (QNCs) were prepared in this study. METHODS: QNCs were prepared by a 100 µm diameter Y-shape microfluidic channel. Some impact factors affecting the generation of QNCs such as concentration and flow rate were investigated. Furthermore, the fluid mixing in the microfluidic channel was simulated by fluid software. RESULTS: XRPD and DSC analyses indicated that the prepared QNCs were amorphous. Stable QNCs with a particle size of 77.9 ± 3.63 nm and polydispersity index of 0.26 ± 0.02 were obtained. TEM showed that the as-prepared QNCs had a uniform spherical shape with an average particle size of about 100-300 nm. In the dissolution medium without cosolvent Tween -80, the dissolution of QCT was poor, its final accumulated dissolution was only 3.95%, while that of QNCs was 66%. CONCLUSION: When QCT was changed to QNCs by microfluidic technology, its dissolution property could be obviously improved. Therefore, microfluidic technology as a new method to prepare nanocrystals has a good applying prospect in improving dissolution property for poorly water-soluble drugs.

Bioaccessibility of lead and cadmium in soils around typical lead-acid power plants and their effect on gut microorganisms.

Potentially toxic elements (Pb and Cd) contamination of soil can adversely affect human health. Moreover, these metal ions interact with the gut microbiota after entering the human digestive system. Based on the physiologically based extraction test and the simulator of human intestinal microbial ecosystem, the bioaccessibility of Pb and Cd in soils contaminated with lead-acid power plants was assessed. The gastric stage exhibited the greatest average bioaccessibility of lead and cadmium (63.39% and 57.22%), followed by the small intestinal stage (6.86% and 36.29%); due to gut microorganisms, the bioaccessibility of lead and cadmium was further reduced in the colon stage (1.86% and 4.22%). Furthermore, to investigate soil contamination's effects on gut microbes, 16S rRNA high-throughput sequencing was used to identify the gut microbial species after the colon period. Due to Pb and Cd exposure, the relative abundance of Firmicutes and unidentified_Bacteria decreased, while the relative abundance of Proteobacteria, Synergistota, and Bacteroidota increased. The relationship between environmental factors and the number of microbial species in the gut was also examined using Spearman correlation analysis. Pb and Cd exposure has been found to affect the composition and structure of the gut microbiota.

[Clinical and genetic characteristics of four children with Kabuki syndrome due to de novo variants of KMT2D gene].

OBJECTIVE: To explore the clinical and genetic characteristics of four children with Kabuki syndrome (KS) due to variants of KMT2D gene. METHODS: Four children with KS diagnosed at the Children's Hospital of Shanxi Province between January 2020 and December 2022 were selected as the study subjects. Whole exome sequencing was carried out for the children and their family members. Candidate variants were verified by Sanger sequencing and pathogenicity analysis. RESULTS: The KS phenotype scores for the four children were 7, 8, 6, and 6, respectively. Child 2 also presented with a rare solitary kidney malformation. Genetic testing revealed that all children had harbored novel de novo variants of the KMT2D gene, including c.16472_16473del, c.858dup, c.11899C>T, and c.12844C>T, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were classified as pathogenic. CONCLUSION: For children showing phenotypes such as distinctive facial features, intellectual disability, developmental delay, cardiac abnormalities, and urinary system anomalies, KS should be considered. Early diagnosis and intervention can be achieved through genetic testing, especially in the presence of KMT2D gene mutations.

Exploring the spatial effects and influencing mechanism of ozone concentration in the Yangtze River Delta urban agglomerations of China.

Ground-level ozone (O3) pollution has emerged as a significant concern impacting air quality in urban agglomerations, primarily driven by meteorological conditions and social-economic factors. However, previous studies have neglected to comprehensively reveal the spatial distribution and driving mechanism of O3 pollution. Based on the O3 monitoring data of 41 cities in the Yangtze River Delta (YRD) from 2014 to 2021, a comprehensive analysis framework of spatial analysis-spatial econometric regression was constructed to reveal the driving mechanism of O3 pollution. The results revealed the following: (1) O3 concentrations in the YRD exhibited a general increasing and then decreasing trend, indicating an improvement in pollution levels. The areas with higher O3 concentration are mainly the cities concentrated in central and southern Jiangsu, Shanghai, and northern Zhejiang. (2) The change of O3 concentration and distribution is the result of various factors. The effect of urbanization on O3 concentrations followed an inverted U-shaped curve, which implies that achieving higher quality urbanization is essential for effectively controlling urban O3 pollution. Traffic conditions and energy consumption have significant direct positive influences on O3 concentrations and spatial spillover effects. The indirect pollution contribution, considering economic weight, accounted for about 35%. Thus, addressing overall regional energy consumption and implementing traffic source regulations are crucial paths for O3 pollution control in the YRD. (3) Meteorological conditions play a certain role in regulating the O3 concentration. Higher wind speed will promote the diffusion of O3 and increase the O3 concentration in the surrounding city. These findings provide valuable insights for designing effective policies to improve air quality and mitigate ozone pollution in urban agglomeration area.

Upgrading the genome of an elite japonica rice variety Kongyu 131 for lodging resistance improvement.

Developing a new rice variety requires tremendous efforts and years of input. To improve the defect traits of the excellent varieties becomes more cost and time efficient than breeding a completely new variety. Kongyu 131 is a high-performing japonica variety with early maturity, high yield, wide adaptability and cold resistance, but the poor-lodging resistance hinders the industrial production of Kongyu 131 in the Northeastern China. In this study, we attempted to improve the lodging resistance of Kongyu 131 from perspectives of both gene and trait. On the one hand, by QTL analysis and fine mapping we discovered the candidate gene loci. The following CRISPR/Cas9 and transgenic complementation study confirmed that Sd1 dominated the lodging resistance and favourable allele was mined for precise introduction and improvement. On the other hand, the Sd1 allelic variant was identified in Kongyu 131 by sequence alignment, then introduced another excellent allelic variation by backcrossing. Then, the two new resulting Kongyu 131 went through the field evaluation under different environments, planting densities and nitrogen fertilizer conditions. The results showed that the plant height of upgraded Kongyu 131 was 17%-26% lower than Kongyu 131 without penalty in yield. This study demonstrated a precise and targeted way to update the rice genome and upgrade the elite rice varieties by improving only a few gene defects from the perspective of breeding.

Path sampling and integration method to calculate speckle patterns.

A stable speckle pattern is generated when a coherent beam illuminates a stationary scattering medium that contains numerous scatterers with fixed positions. To date, there has been no valid method to the best of our knowledge for calculating the speckle pattern of a macro medium with a large number of scatterers. Here, a new method based on possible path sampling with corresponding weights and coherent superposition is presented for the simulation of optical field propagation in a scattering medium and output speckle patterns. In this method, a photon is launched onto a medium with fixed scatterers. It propagates in one direction; upon collision with a scatterer, its direction is updated. The procedure is repeated until it exits the medium. A sampled path is obtained in this manner. By repeatedly launching photons, numerous independent optical paths can be sampled. A speckle pattern, corresponding to the probability density of the photon, is formed by the coherent superposition of sufficiently sampled path lengths ending on a receiving screen. This method can be used in sophisticated studies of the influences of medium parameters, motion of scatterers, sample distortions on speckle distributions, and morphological appearances. It can be used for micro-examination of optical fields in scattering media and may inspire new methods and techniques for non-invasive precision detection and diagnosis of scattering media.

FSTL3 partially mediates the association of increased nonalcoholic fatty liver disease fibrosis risk with acute myocardial infarction in patients with type 2 diabetes mellitus.

BACKGROUND: The study aimed to investigate an association of increased liver fibrosis with acute myocardial infarction (AMI), and to investigate the mediating effect of serum follistatin-like protein 3 (FSTL3) on the association in patients with type 2 diabetes mellitus (T2DM). METHOD: A total of 1424 participants were included in this study, and were firstly divided into two groups: 429 T2DM patients and 995 T2DM patients with NAFLD to assess the association of NAFLD and AMI. Then 995 T2DM co-existent NAFLD patients were categorized by NAFLD fibrosis risk to explore the association between NAFLD fibrosis risk and AMI. Immunohistochemistry staining and semi-quantitative analysis of liver FSTL3 were performed in 60 patients with NAFLD. There were 323 individuals (191 without AMI and 132 with AMI) in T2DM co-existent NAFLD patients who had serum samples, and serum FSTL3 was tested and mediation effect of FSTL3 in association of NAFLD fibrosis and AMI was performed. RESULTS: First, increased NAFLD fibrosis risk was an independent risk factor for AMI in patients with T2DM and co-existent NAFLD. In addition, analysis of Gene Expression Omnibus (GEO) database and immunohistochemical staining confirmed the increased expression of FSTL3 in the liver of NAFLD patients with fibrosis. Serum FSTL3 significantly increased in patients with high NAFLD fibrosis risk and AMI, and closely associated with NAFLD fibrosis and AMI severity in T2DM patients with co-existent NAFLD. Most importantly, analysis of the level of mediation revealed that increased serum FSTL3 partially mediated the association of increased NAFLD fibrosis risk with AMI in T2DM patients with co-existent NAFLD. CONCLUSIONS: NAFLD fibrosis was closely associated with AMI in T2DM patients. FSTL3 expression was enriched in the liver of NAFLD patients with significant and advanced fibrosis, and serum FSTL3 partially mediated the association of increased liver fibrosis risk with AMI in T2DM patients.