GC-MS based antioxidants characterization in Saussurea heteromalla (D. Don) Hand-Mazz by inhibition of nitric oxide generation in macrophages.

For centuries, medicinal plants have served as the cornerstone for traditional health care systems and same practice is still prevalent today. In the Himalayan region, Saussurea heteromalla holds a significant place in traditional medicine and is used to address various health issues. Despite its historical use, little exploration has focused on its potential for scavenging free radicals and reducing inflammation. Hence, our current study aims to investigate the free radical scavenging capabilities of S. heteromalla extracts. The n-hexane extract of entire plant revealed promising activity. This extract underwent extensive extraction on a larger scale. Subsequent purification, employing column chromatography, HPLC-DAD techniques, led to the identification of active compounds, confirmed via GC-MS and the NIST database as 1-O-butyl 2-O-octyl benzene-1,2-dicarboxylate and 2,4-ditert-butylphenol. Assessing the free radical scavenging properties involved utilizing RAW-264.7 macrophages activated by lipopolysaccharides. Notably, the compound 2,4-di-tert-butylphenol exhibited remarkable scavenging abilities, demonstrating over 80% inhibition of Nitric oxide. This study stands as the inaugural report on the isolation of these compounds from S. heteromalla.

Health-promoting compounds in Amomum villosum Lour and Amomum tsao-ko: Fruit essential oil exhibiting great potential for human health.

The Zingiberaceae family serves as a diverse repository of bioactive phytochemicals, comprising approximately 52 genera and 1300 species of aromatic perennial herbs distinguished by their distinct creeping horizontal or tuberous rhizomes. Amomum villosum Lour. and Amomum tsao-ko Crevost & Lemaire., are the important plants of family Zingiberaceae that have been widely used in traditional medicine for the treatment of many ailments. The Amomum species are employed for their aromatic qualities and are valued as spices and flavorings. In the essential oils (EOs) of Amomum species, notable constituents include, camphor, methyl chavicol, bornyl acetate, trans-p-(1-butenyl) anisole, α-pinene, and ß-pinene. OBJECTIVE: The aim of this review is to present an overview of pharmacological studies pertaining to the extracts and secondary metabolites isolated from both species. The foremost objective of review is not only to increase the popularity of Amomum as a healthy food choice but also to enhance its status as a staple ingredient for the foreseeable future. RESULT: We endeavored to gather the latest information on antioxidant, antidiabetic, anticancer, antiobesity, antimicrobial, and anti-inflammatory properties of plants as well as their role in neuroprotective diseases. Research conducted through in-vitro studies, animal model, and compounds analysis have revealed that both plants exhibit a diverse array health promoting properties. CONCLUSION: the comprehensive review paper provides valuable insights into the diverse range of bioactive phytochemicals found in A. villosum and A. tsao-ko, showcasing their potential in preventing diseases and promoting overall human well-being. The compilation of information on their various health-enhancing properties contributes to the broader understanding of these plants and their potential applications in traditional medicine and beyond.

Geographic differences and variation of functional components of brown rice in 690 mini-core collections from global germplasms.

Objective: To understand the geographic differences and variations in the functional components of brown rice cores collected from global rice germplasms. Methods: Four functional components, γ-aminobutyric acid (GABA), resistant starch (RS), total flavonoids, and alkaloids, in brown rice from 690 mini-core collections from 31 countries from five continents and the International Rice Research Institute, were analyzed using a spectrophotometry colorimetric method, and the results were statistically validated. Conclusion: The highest average amounts of functional components were obtained in Asian germplasms, except for GABA, and total flavonoids were highest in brown rice from Europe and Oceania, followed by Asia. The highest coefficient of variation for GABA was observed in Asia; that for RS and total flavonoids was observed in Africa, followed by Asia; and that for alkaloids was observed in America, followed by Asia. Overall, Asian countries were the most prominent and representative zones with the highest genotypic potential for functional components of brown rice. Forty-one rice accessions with enriched functional components originated mostly from biodiversity-rich areas in China, followed by those in the Philippines. Late sowing favored the enrichment of these components in brown rice. The current study provides a reference for rice breeding with enriched functional constituents, and guidelines for screening functional rice that could be used for human chronic disease research.

Genome-Wide Association Study Reveals the Genetic Basis of Total Flavonoid Content in Brown Rice.

Flavonoids have anti-inflammatory, antioxidative, and anticarcinogenic effects. Breeding rice varieties rich in flavonoids can prevent chronic diseases such as cancer and cardio-cerebrovascular diseases. However, most of the genes reported are known to regulate flavonoid content in leaves or seedlings. To further elucidate the genetic basis of flavonoid content in rice grains and identify germplasm rich in flavonoids in grains, a set of rice core collections containing 633 accessions from 32 countries was used to determine total flavonoid content (TFC) in brown rice. We identified ten excellent germplasms with TFC exceeding 300 mg/100 g. Using a compressed mixed linear model, a total of 53 quantitative trait loci (QTLs) were detected through a genome-wide association study (GWAS). By combining linkage disequilibrium (LD) analysis, location of significant single nucleotide polymorphisms (SNPs), gene expression, and haplotype analysis, eight candidate genes were identified from two important QTLs (qTFC1-6 and qTFC9-7), among which LOC_Os01g59440 and LOC_Os09g24260 are the most likely candidate genes. We also analyzed the geographic distribution and breeding utilization of favorable haplotypes of the two genes. Our findings provide insights into the genetic basis of TFC in brown rice and could facilitate the breeding of flavonoid-rich varieties, which may be a prevention and adjuvant treatment for cancer and cardio-cerebrovascular diseases.

Validation of the JAMR F1701T (arm type) pressure monitor according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/ISO 81060-2:2018 protocol.

To validate the JAMR F1701T (arm type) blood pressure (BP) monitor according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060-2:2018). A total of 90 subjects (male 60 and female 30) were recruited to fulfill the criteria of the AAMI/ESH/ISO Universal Standard (the number, gender, age, limber size, and BP distribution), and sequential measurements of BP, including both SBP and DBP were obtained using the test device and the standard mercury sphygmomanometer. A total of 270 sets of comparison data (three sets of each subject) were obtained and analyzed. According to the validation criterion 1 of ISO 81060-2:2018, the mean ± SD of the differences between the JAMR F1701T and mercury sphygmomanometer BP (systolic/diastolic) readings was 2.06 ± 6.83/-4.84 ± 5.23 mmHg. For criterion 2, the SD of the averaged BP (systolic/diastolic) differences between the JAMR F1701 and reference BP (systolic/diastolic) per participant was 5.62/4.39 mmHg (the requirement was ≤6.43/5.01 mmHg by calculation). The JAMR F1701T met all the requirements of the ISO 81060-2:2018, and can be recommended for clinical and self/home use.

Keyword-Based Diverse Image Retrieval With Variational Multiple Instance Graph.

The task of cross-modal image retrieval has recently attracted considerable research attention. In real-world scenarios, keyword-based queries issued by users are usually short and have broad semantics. Therefore, semantic diversity is as important as retrieval accuracy in such user-oriented services, which improves user experience. However, most typical cross-modal image retrieval methods based on single point query embedding inevitably result in low semantic diversity, while existing diverse retrieval approaches frequently lead to low accuracy due to a lack of cross-modal understanding. To address this challenge, we introduce an end-to-end solution termed variational multiple instance graph (VMIG), in which a continuous semantic space is learned to capture diverse query semantics, and the retrieval task is formulated as a multiple instance learning problems to connect diverse features across modalities. Specifically, a query-guided variational autoencoder is employed to model the continuous semantic space instead of learning a single-point embedding. Afterward, multiple instances of the image and query are obtained by sampling in the continuous semantic space and applying multihead attention, respectively. Thereafter, an instance graph is constructed to remove noisy instances and align cross-modal semantics. Finally, heterogeneous modalities are robustly fused under multiple losses. Extensive experiments on two real-world datasets have well verified the effectiveness of our proposed solution in both retrieval accuracy and semantic diversity.

Conferring of drought tolerance in wheat (Triticum aestivum L.) genotypes using seedling indices.

Wheat is the most widely grown and consumed crop because of its economic and social benefits. This crop is more important globally for food and feed, and its productivity is particularly vulnerable to abiotic factors. In this study, 40 wheat genotypes were studied to access the drought tolerance level using completely randomized design (CRD) in 250 ml disposable cups through morpho-physiological attributes at seedling stage. The wheat germplasm was tested under normal and two drought stress level D1 (50% field capacity) and D2 (75% field capacity) for different seedling attributes such as germination percentage (GP), chlorophyll content (CC), shoot length (SL), root length (RL), shoot fresh weight (SFW), root fresh weight (RFW), seedling fresh weight (SDFW), shoot dry weight (SDW), root dry weight (RDW), relative water content (RWC), root/shoot ratio (RS), and seedling dry weight (SeDW). The results of analysis of variance (ANOVA) and spider analysis indicate that significant amount of genetic variation was present and behavior of studied germplasm showed different behavior in different environment. The correlation analysis showed that root length has significantly positive association with root/shoot ratio, dry weight, and fresh weight while negatively correlated with shoot length and relative water content. Based on the positively associated traits, the studied genetic material would improve genetic gain for drought tolerance. The multivariate analysis showed that out 13 principal components only five PCs were significant and has eigenvalue > 1, cumulatively showed 82.33, 83.07, and 97.34% of total variation under normal, D1 and D2 conditions, respectively. Significantly, the result of spider graph and multivariate analysis showed that genotypes G47, G48, G65, G68, and G80 performed well in all drought stress conditions and considered as drought-tolerant genotypes. The best performing genotypes can be used in future breeding programs. The selection on the bases of studied attributes is effective for development of drought-tolerant and high-yielding varieties for sustainable food security.

Characterization of wheat (Triticum aestivum L.) accessions using morpho-physiological traits under varying levels of salinity stress at seedling stage.

Abiotic stresses are the major stressors affecting wheat (Triticum aestivum L.) production worldwide. The world population is increasing continuously. It is very difficult to feed the population because one-third world's population consumes wheat as a staple food. Among all abiotic stresses, salinity is one that led to a drastic reduction in wheat crop fitness and productivity. Thus, understanding the effects of salinity stress becomes indispensable for wheat improvement programs which have depended mainly on the genetic variations present in the wheat genome through conventional breeding. Therefore, an experiment was conducted using a complete randomized design with four replications, to determine the selection criteria for salinity-tolerant germplasm based on morphophysiological traits at the seedling stage. Three levels of salt solutions, i.e., 4, 8, and 12 dSm-1 were applied and the performance of different genotypes under these three salinities levels was observed. Results depicted that leaf water content and relative water content were correlated with each other. Notably, selection based on these traits increased the performance of other characters. The genotypes G11, G13, G18, G22, and G36 performed best in the salinity stress. So, these genotypes are considered salinity-tolerant genotypes. The genotypes G4, G17, G19, G30, and G38 performed worst in the stress and these were salinity-susceptible genotypes. From the results of the principal component (PC) analysis, the first five PCs were indicated to have a substantial genetic variation from the total of 14 PCs. These PCs showed 75, 73, 65.324, and 65.162% of total variation under normal, salinity level 4, 8, and 12 dSm-1, respectively. Stomatal conductance, fresh shoot weight and fresh root weight, and dry shoot weight and dry root weight were not significant and negatively associated with all other traits studied, except for relative water and leaf water content. Overall, the results suggested that selection based on leaf water content and relative water content at the seedling stage would genetically improve salinity tolerance. Genotypes with good performance under salt stress conditions may be useful in future breeding programs and will be effective in developing high-yielding salt-tolerant wheat varieties.

Actional Mechanisms of Active Ingredients in Functional Food Adlay for Human Health.

Medicinal and food homologous adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) plays an important role in natural products promoting human health. We demonstrated the systematic actional mechanism of functional ingredients in adlay to promote human health, based on the PubMed, CNKI, Google, and ISI Web of Science databases from 1988 to 2022. Adlay and its extracts are rich in 30 ingredients with more than 20 health effects based on human and animal or cell cultures: they are anti-cancer, anti-inflammation, anti-obesity, liver protective, anti-virus, gastroprotective, cardiovascular protective, anti-hypertension, heart disease preventive, melanogenesis inhibiting, anti-allergy, endocrine regulating, anti-diabetes, anti-cachexia, osteoporosis preventive, analgesic, neuroprotecting, suitable for the treatment of gout arthritis, life extending, anti-fungi, and detoxifying effects. Function components with anti-oxidants are rich in adlay. These results support the notion that adlay seeds may be one of the best functional foods and further reveal the action mechanism of six major functional ingredients (oils, polysaccharides, phenols, phytosterols, coixol, and resistant starch) for combating diseases. This review paper not only reveals the action mechanisms of adding adlay to the diet to overcome 17 human diseases, but also provides a scientific basis for the development of functional foods and drugs for the treatment of human diseases.

Gene silencing, knockout and over-expression of a transcription factor ABORTED MICROSPORES (SlAMS) strongly affects pollen viability in tomato (Solanum lycopersicum).

BACKGROUND: The tomato (Solanum lycopersicum L.) is an economically valuable crop grown worldwide. Because the use of sterile males reduces the cost of F1 seed production, the innovation of male sterility is of great significance for tomato breeding. The ABORTED MICROSPORES gene (AMS), which encodes for a basic helix-loop-helix (bHLH) transcription factor, has been previously indicated as an essential gene for tapetum development in Arabidopsis and rice. To determine the function of the SlAMS gene (AMS gene from S. lycopersicum) and verify whether it is a potential candidate gene for generating the male sterility in tomato, we used virus-induced gene silencing (VIGS), CRISPR/Cas9-mediated genome editing and over-expression technology to transform tomato via Agrobacterium infection. RESULTS: Here, the full-length SlAMS gene with 1806 bp from S. lycopersicum (Accession No. MK591950.1) was cloned from pollen cDNA. The results of pollen grains staining showed that, the non-viable pollen proportions of SlAMS-silenced (75%), -knockouted (89%) and -overexpressed plants (60%) were significantly higher than the wild type plants (less than 10%; P < 0.01). In three cases, the morphology of non-viable pollen grains appeared tetragonal, circular, atrophic, shriveled, or otherwise abnormally shaped, while those of wild type appeared oval and plump. Furthermore, the qRT-PCR analysis indicated that SlAMS in anthers of SlAMS-silenced and -knockouted plants had remarkably lower expression than in that of wild type (P < 0.01), and yet it had higher expression in SlAMS-overexpressed plants (P < 0.01). CONCLUSION: In this paper, Our research suggested alternative approaches to generating male sterility in tomato, among which CRISPR/Cas9-mediated editing of SlAMS implied the best performance. We also demonstrated that the downregulation and upregulation of SlAMS both affected the pollen formation and notably led to reduction of pollen viability, suggesting SlAMS might be essential for regulating pollen development in tomato. These findings may facilitate studies on clarifying the SlAMS-associated molecular regulatory mechanism of pollen development in tomato.

Genome-wide association mapping of bread wheat genotypes for sustainable food security and yield potential under limited water conditions.

Determining the genetic basis of yield and water deficient tolerance in wheat is vital for wheat breeding programs. Herein, a genome-wide association study (GWAS) was performed for water deficient and yield-related attributes on wheat genotypes with high-density Illumina 90K Infinium SNP array. Major yield and drought-related attributes were phenotyped on a panel of Pakistani and foreign accessions grown in non-stressed and water deficient stressed environments during two crop cycles. Among all accessions, highly significant variations were shown in studied environments for examined characters. Water deficient conditions, reduced the wheat yield and had strong and positive correlation among relative water content and grain yield per plant. Population structure analyses based on 90,000 SNP data, classify the accessions into 4 sub-populations. Marker-trait association analyses (MTA) revealed that 134 significant SNPs were linked with yield and drought tolerance attributes. Pleotropic loci RAC875_s117925_244 and RAC875_c16333_340 located on chromosome 5A and 2A respectively, were significantly linked with relative water contents (RWC), cell membrane thermo-stability (CMT), grain per spike (GPS), spikelet per spike (SPS) and grain yield per plant (GYP). The markers Ra_c58279_684, BobWhite_c23828_341 and IAAV3414 located on chromosomes 2A, 6B and 7B respectively, showed pleotropic effects for RWC, GPS and GYP under both environments. The current experiment not only validated several MTAs reported in other studies but also discovered novel MTAs which significant under drought-stressed conditions. A total of 171 candidate genes were recognized that could be cloned and functionally characterized for the respective associated traits. For RWC and CMT, total 11 and 3 associated SNPs were mapped on coding DNA sequence (CDS) of the identified candidate genes. Isolation and characterization of the candidate genes herein mapped SNPs will be useful in discovering novel genes underpinning drought tolerance in bread wheat to fulfill the wheat demand and sustainable food security under limited water conditions.

Social-path embedding-based transformer for graduation development prediction.

As the education of students attracts more and more attention, the task of graduation development prediction has gradually become a hot topic in academia and industry. The task of graduation development prediction aims to predict the employment category of students in advance via academic achievement data, which can help administrators understand students' learning status and set up a reasonable learning plan. However, existing research ignores the potential impact of social relationships on students' graduation development choices. To fully explore social relationships among students, we propose a Social-path Embedding-based Transformer Neural Network (SPE-TNN) for the task of graduation development prediction in this paper. Specifically, SPE-TNN is divided into the Social-path selection layer, the Social-path embedding layer, the Transformer layer, and the Multi-layer projection layer. Firstly, the Social-path selection layer is designed to find social relationships that impact graduation development and embed them into the student's performance features through the Social-path embedding layer. Secondly, the Transformer layer is adopted to balance the weights of the students' features. Finally, the Multi-layer projection layer is used to achieve the student graduation development prediction. Experimental results on the real-world datasets show that SPE-TNN outperforms the existing popular approaches.

Genome-wide association mapping for high temperature tolerance in wheat through 90k SNP array using physiological and yield traits.

Dissecting the genetic basis of physiological and yield traits against tolerance to heat stress is an essential in wheat breeding programs to boost up the wheat yield for sustainable food security. Herein, a genome-wide association study (GWAS) was performed to reveal the genetic basis of heat tolerance using high-density Illumina 90K Infinium SNPs array through physiological and yield indices. These indices were phenotyped on a diverse panel of foreign and domestic genotypes of Pakistan, grown in normal and heat-stressed environments. Based on STRUCTURE analysis, the studied germplasm clustered into four sub-population. Highly significant variations with a range of moderate (58.3%) to high (77.8%) heritability was observed under both conditions. Strong positive correlation existed among physiological and yield related attributes. A total of 320 significant (-log10 P ≥ 3) marker-trait associations (MTAs) were identified for the observed characters. Out of them 169 and 151 MTAs were recorded in normal and heat stress environments, respectively. Among the MTA loci, three (RAC875_c103017_302, Tdurum_contig42087_1199, and Tdurum_contig46877_488 on chromosomes 4B, 6B, and 7B respectively), two (BobWhite_c836_422 and BS00010616_51) and three (Kukri_rep_c87210_361, D_GA8KES401BNLTU_253 and Tdurum_contig1015_131) on chromosomes 5A, 1B, and 3D at the positions 243.59cM, 77.82cM and 292.51cM) showed pleiotropic effects in studied traits under normal, heat-stressed and both conditions respectively. The present study not only authenticated the numerous previously reported MTAs for examined attributes but also revealed novel MTAs under heat-stressed conditions. Identified SNPs will be beneficial in determining the novel genes in wheat to develop the heat tolerant and best yielded genotypes to fulfill the wheat requirement for the growing population.

Genome-wide association mapping of bread wheat genotypes using yield and grain morphology-related traits under different environments.

Depleting water resources and increasing global temperature due to climate change are major challenges to agriculture and food security worldwide. Deciphering the underlying mechanisms of traits contributing to grain development and yield is essential for the development of climate-resilient cultivars. Therefore, this study assessed 105 bread wheat genotypes grown under control, drought, and heat-stress conditions for two crop seasons and performed a genome-wide association study (GWAS) using a 90k SNP array. The genotypes showed significant trait differences under all environmental conditions. Highly significant variation was observed, with moderate (50.09%) to high (76.19%) heritability in the studied germplasms. The studied traits were all also significantly positively correlated. A total of 541 significant associations (p ≤ 10-3) between marker and trait (MTAs) were observed after crossing the FDR <0.05 threshold for all traits. Among these, 195, 179, and 167 significant MTAs were detected under control, drought, and heat-stress conditions, respectively. Under the control and drought conditions, pleiotropic loci BS00010616_51 and BS00010868_51 were observed on chromosomes 7B and 1B situated at 186.24 cM and 35.47 cM, respectively. Pleiotropic loci BS00010868_51, Kukri_c11154_1723, and Ex_c10068_1509 were identified on chromosomes 1B, 5B, and 2A, respectively, under control and heat stress conditions. A stable and consistent locus (Excalibur_c20796_395) on chromosome 7A, located at 372.34 cM, was also linked to grain morphology and yield-related attributes in control, drought, and heat-stress conditions. The results of the current study confirmed several previously reported MTAs for the traits under consideration and identified new MTAs under harsh climatic conditions. These SNPs will aid in the discovery of novel genes in wheat. SNPs showing significant associations may be used in marker-assisted selection and allow the development of drought- and heat-tolerant genotypes with high yields to address global food security concerns.

NILs of Cold Tolerant Japonica Cultivar Exhibited New QTLs for Mineral Elements in Rice.

Chilling stress at booting stage can cause floret deterioration and sterility by limiting the supply of food chain and the accumulation of essential mineral elements resulting in reduction of yield and grain quality attributes in rice. Genomic selection of chilling tolerant rice with reference to the accumulation of mineral elements will have great potential to cope with malnutrition and food security in times of climate change. Therefore, a study was conducted to explore the genomic determinants of cold tolerance and mineral elements content in near-isogenic lines (NILs) of japonica rice subjected to chilling stress at flowering stage. Detailed morphological analysis followed by quantitative analysis of 17 mineral elements revealed that the content of phosphorus (P, 3,253 mg/kg) and potassium (K, 2,485 mg/kg) were highest while strontium (Sr, 0.26 mg/kg) and boron (B, 0.34 mg/kg) were lowest among the mineral elements. The correlation analysis revealed extremely positive correlation of phosphorus (P) and copper (Cu) with most of the cold tolerance traits. Among all the effective ear and the second leaf length correlation was significant with half of the mineral elements. As a result of comparative analysis, some QTLs (qBRCC-1, qBRCIC-2, qBRZC-6, qBRCHC-6, qBRMC-6, qBRCIC-6a, qBRCIC-6b, qBRCHC-6, and qBRMC-6) identified for calcium (Ca), zinc (Zn), chromium (Cr) and magnesium (Mg) on chromosome number 1, 2, and 6 while, a novel QTL (qBCPC-1) was identified on chromosome number 1 for P element only. These findings provided bases for the identification of candidate genes involved in mineral accumulation and cold tolerance in rice at booting stage.

Construction of a Multifunctional Nano-Scale Metal-Organic Framework-Based Drug Delivery System for Targeted Cancer Therapy.

The antitumor activity of triptolide (TP) has received widespread attention, although its toxicity severely limits its clinical application. Therefore, the design of a targeted drug delivery system (TDDS) has important application prospects in tumor treatment. Metal-organic frameworks (MOFs), with high drug-carrying capacity and good biocompatibility, have aroused widespread interest for drug delivery systems. Herein, folic acid (FA) and 5-carboxylic acid fluorescein (5-FAM) were used to modify Fe-MIL-101 to construct a functionalized nano-platform (5-FAM/FA/TP@Fe-MIL-101) for the targeted delivery of the anti-tumor drug triptolide and realize in vivo fluorescence imaging. Compared with Fe-MIL-101, functionalized nanoparticles not only showed better targeted therapy efficiency, but also reduced the systemic toxicity of triptolide. In addition, the modification of 5-FAM facilitated fluorescence imaging of the tumor site and realized the construction of an integrated nano-platform for fluorescence imaging and treatment. Both in vitro and in vivo studies of functionalized nanoparticles have demonstrated excellent fluorescence imaging and synergistic targeting anticancer activity with negligible systemic toxicity. The development of functional nano-platform provides new ideas for the design of MOF-based multifunctional nano-drug delivery system, which can be used for precise treatment of tumor.

PEGylated Nanoscale Metal-Organic Frameworks for Targeted Cancer Imaging and Drug Delivery.

Nanoscale metal-organic frameworks (nMOFs) are a unique type of hybrid materials, which are broadly applicable as cargo delivery systems. However, the relatively low material stability and insufficient cancer cell interacting capacity have limited nMOFs' applications in cancer theranostics. Herein, a zirconium-based nMOF UiO-66-N3 was synthesized, and its surface was covalently functionalized with alkyne-containing polyethylene glycol (PEG) via the azide-alkyne click chemistry. After that, F3 peptide was attached for targeting of cancer cells (the material was denoted as UiO-66-PEG-F3). Doxorubicin (DOX) served as a therapeutic drug and a fluorescent label in this study, and it was transported into UiO-66-PEG conjugates with sufficient drug loading efficiency. pH-responsive release of DOX from UiO-66 conjugates was witnessed. The structural integrity of UiO-66-N3 was maintained post the surface modification process. Flow cytometry and confocal fluorescence microscopy revealed that DOX/UiO-66-PEG-F3 had stronger accumulation in MDA-MB-231 cells (nucleolin+) compared with DOX/UiO-66-PEG. In order to track the pharmacokinetic behavior (organ distribution profile) in vivo, the positron-emitting zirconium-89 (89Zr) was incorporated into UiO-66-N3. Similar PEGylation and F3 peptide conjugation resulted in the formation of 89Zr-UiO-66-PEG-F3. Serial positron emission tomography (PET) imaging demonstrated that the preferential accumulation of 89Zr-UiO-66-PEG-F3 in MDA-MB-231 tumors, and their liver clearance was faster than PEGylated UiO-66 using noncovalent methods. Thus, the PEGylated nMOFs using covalent strategies may find broad application in future cancer theranostics.

Stepwise selection of natural variations at CTB2 and CTB4a improves cold adaptation during domestication of japonica rice.

The improvement of cold adaptation has contributed to the increased growing area of rice. Standing variation and de novo mutation are distinct natural sources of beneficial alleles in plant adaptation. However, the genetic mechanisms and evolutionary patterns underlying these sources in a single population during crop domestication remain elusive. Here we cloned the CTB2 gene, encoding a UDP-glucose sterol glucosyltransferase, for cold tolerance in rice at the booting stage. A single standing variation (I408V) in the conserved UDPGT domain of CTB2 originated from Chinese Oryza rufipogon and contributed to the cold adaptation of Oryza sativa ssp. japonica. CTB2 is located in a 56.8 kb region, including the previously reported gene CTB4a in which de novo mutation arose c. 3200 yr BP in Yunnan province, China, conferring cold tolerance. Standing variation of CTB2 and de novo mutation of CTB4a underwent stepwise selection to facilitate cold adaptation to expand rice cultivation from high-altitude to high-latitude regions. These results provide an example of stepwise selection on two kinds of variation and describe a new molecular mechanism of cold adaptation in japonica rice.

Hypericin-mediated photodynamic therapy for the treatment of cancer: a review.

OBJECTIVES: Hypericin is a polycyclic aromatic naphthodianthrone that occurs naturally. It is also an active ingredient in some species of the genus Hypericum. Emerging evidence suggests that hypericin has attracted great attention as a potential anticancer drug and exhibits remarkable antiproliferative effect upon irradiation on various tumour cells. This paper aims to summarise the anticancer effect and molecular mechanisms modulated by hypericin-medicated photodynamic therapy and its potential role in the cancer treatment. KEY FINDINGS: Hypericin-medicated photodynamic therapy could inhibit the proliferation of various tumour cells including bladder, colon, breast, cervical, glioma, leukaemia, hepatic, melanoma, lymphoma and lung cancers. The effect is primarily mediated by p38 mitogen-activated protein kinase (MAPK), JNK, PI3K, CCAAT-enhancer-binding protein homologous protein (CHOP)/TRIB3/Akt/mTOR, TRAIL/TRAIL-receptor, c-Met and Ephrin-Eph, the mitochondria and extrinsic signalling pathways. Furthermore, hypericin-medicated photodynamic therapy in conjunction with chemotherapeutic agents or targeted therapies is more effective in inhibiting the growth of tumour cells. SUMMARY: During the past few decades, the anticancer properties of photoactivated hypericin have been extensively investigated. Hypericin-medicated photodynamic therapy can modulate a variety of proteins and genes and exhibit a great potential to be used as a therapeutic agent for various types of cancer.

A Multi-Feature Fusion Slam System Attaching Semantic In-Variant to Points and Lines.

The traditional simultaneous localization and mapping (SLAM) system uses static points of the environment as features for real-time localization and mapping. When there are few available point features, the system is difficult to implement. A feasible solution is to introduce line features. In complex scenarios containing rich line segments, the description of line segments is not strongly differentiated, which can lead to incorrect association of line segment data, thus introducing errors into the system and aggravating the cumulative error of the system. To address this problem, a point-line stereo visual SLAM system incorporating semantic invariants is proposed in this paper. This system improves the accuracy of line feature matching by fusing line features with image semantic invariant information. When defining the error function, the semantic invariant is fused with the reprojection error function, and the semantic constraint is applied to reduce the cumulative error of the poses in the long-term tracking process. Experiments on the Office sequence of the TartanAir dataset and the KITTI dataset show that this system improves the matching accuracy of line features and suppresses the cumulative error of the SLAM system to some extent, and the mean relative pose error (RPE) is 1.38 and 0.0593 m, respectively.