Genomic insights into local adaptation of upland cotton in China and Pakistan.

KEY MESSAGE: Different kinship and resistance to cotton leaf curl disease (CLCuD) and heat were found between upland cotton cultivars from China and Pakistan. 175 SNPs and 82 InDels loci related to yield, fiber quality, CLCuD, and heat resistance were identified. Elite alleles found in Pakistani accessions aided local adaptation to climatic condition of two countries. Adaptation of upland cotton (Gossypium hirsutum) beyond its center of origin is expected to be driven by tailoring of the genome and genes to enhance yield and quality in new ecological niches. Here, resequencing of 456 upland cotton accessions revealed two distinct kinships according to the associated country. Fiber quality and lint percentage were consistent across kinships, but resistance to cotton leaf curl disease (CLCuD) and heat was distinctly exhibited by accessions from Pakistan, illustrating highly local adaption. A total of 175 SNP and 82 InDel loci related to yield, fiber quality, CLCuD and heat resistance were identified; among them, only two overlapped between Pakistani and Chinese accessions underscoring the divergent domestication and improvement targets in each country. Loci associated with resistance alleles to leaf curl disease and high temperature were largely found in Pakistani accessions to counter these stresses prevalent in Pakistan. These results revealed that breeding activities led to the accumulation of unique alleles and helped upland cotton become adapted to the respective climatic conditions, which will contribute to elucidating the genetic mechanisms that underlie resilience traits and help develop climate-resilient cotton cultivars for use worldwide.

In Situ Fe-Substituted Hexacyanoferrate for High-Performance Aqueous Potassium Ion Batteries.

The eco-friendliness, safety, and affordability of aqueous potassium batteries (AKIBs) have made them popular for large-scale energy storage devices. However, the cycling and rate performance of research materials, particularly cobalt hexacyanoferrate, have yet to meet satisfactory standards. Herein, a room-temperature drafted K1.66 Fe0.25 Co0.75 [Fe(CN)6 ]·0.83H2 O (KFCHCF) sample is reported using an in situ substitution strategy. A higher concentration of ferrocyanide ions decreases the water content and increases the potassium content, while citric acid works as a chelating agent and is responsible for Fe-substitution in the KFCHCF sample. The resultant KFCHCF sample exhibits good rate performance, and about 97% and 90.6% of discharge capacity are conserved after 400 and 1000 cycles at 100 and 200 mA g-1 , respectively. The full cell using the KFCHCF cathode and 1,4,5,8-naphthalenetetracarboxylic dianhydride-derived polyimide (PNTCDA) anode maintains ≈74.93% and 74.35% of discharge capacity at 200 mA g-1 and 1000 mA g-1 for 1000 and >10,000 cycles, respectively. Furthermore, ex situ characterizations demonstrate the high reversibility of K-ions and structural stability during the charge-discharge process. Such high performance is attributed to the fast K-ion migration and crystal structure stabilization caused by in situ Fe-substitution in the KFCHCF sample. Other hexacyanoferrates can be synthesized using this method and used in grid-scale storage systems.

Identification and Immune Characteristics Study of Pyroptosis­Related Genes in Endometriosis.

Endometriosis (EMT) is a prevalent gynecological disorder characterized by pain and infertility associated with the menstrual cycle. Pyroptosis, an emerging cell death mechanism, has been implicated in the pathogenesis of diverse diseases, highlighting its pivotal role in disease progression. Therefore, our study aimed to investigate the impact of pyroptosis in EMT using a comprehensive bioinformatics approach. We initially obtained two datasets from the Gene Expression Omnibus database and performed differential expression analysis to identify pyroptosis-related genes (PRGs) that were differentially expressed between EMT and non-EMT samples. Subsequently, several machine learning algorithms, namely least absolute shrinkage selection operator regression, support vector machine-recursive feature elimination, and random forest algorithms were used to identify a hub gene to construct an effective diagnostic model for EMT. Receiver operating characteristic curve analysis, nomogram, calibration curve, and decision curve analysis were applied to validate the performance of the model. Based on the selected hub gene, differential expression analysis between high- and low-expression groups was conducted to explore the functions and signaling pathways related to it. Additionally, the correlation between the hub gene and immune cells was investigated to gain insights into the immune microenvironment of EMT. Finally, a pyroptosis-related competing endogenous RNA network was constructed to elucidate the regulatory interactions of the hub gene. Our study revealed the potential contribution of a specific PRG to the pathogenesis of EMT, providing a novel perspective for clinical diagnosis and treatment of EMT.

Dosimetric parameters and safety analysis of 3D-printing non-coplanar template-assisted interstitial brachytherapy for non-centrally recurrent cervical cancer.

Introduction: The prognosis of patients with non-central recurrent cervical cancer (NRCC) remains poor, and treatment options are limited. We aimed to explore the accuracy and safety of the 3D-printed non-coplanar template (3D-PNCT)-assisted 192Ir interstitial brachytherapy (ISBT) in the treatment of NRCC. Material and methods: A total of 36 patients with NRCC who received 3D-PNCT-guided 192Ir ISBT in the First Affiliated Hospital of Zhengzhou University from January 2021 to July 2022 were included in this study. There were 36 3D-PNCTs that were designed and printed. The prescribed dose was 30-36 Gy, divided into five to six times, once a week. To evaluate whether the actual parameters were consistent with the preoperative design, the dosimetric parameters of pre- and postoperative treatment plans were compared, including dose of 90% high-risk clinical target volume (HR-CTV D90), volume percentage of 100% and 150% prescribed dose V100% and V150%, homogeneity index (HI), conformal index (CI), external index (EI), and dose received by 2 cm3 (D2cm3) of the rectum, colon, bladder, and ileum. The safety parameters including occurrence of bleeding, infection, pain, radiation enteritis, and radiation cystitis within 3 months after operation were recorded. Results: All patients successfully completed the treatment and achieved the goals of the preoperative plan. There was no significant difference in the accuracy (HRCTVD90, V100%, EI, CI, and HI) and safety (D2cm3 of rectum, colon, bladder, and ileum) parameters of the postoperative plan compared with the preoperative plan (all p>0.05). Major side effects included bleeding at the puncture site (13.9%), postoperative pain (8.3%), acute radiation cystitis (13.9%), and radiation enteritis (19.4%). There were no serious perioperative complications and no grade 3-4 acute radiotherapy side effects. Conclusion: 3D-PNCT-assisted 192Ir ISBT can be accurately and safely applied in the treatment of patients with NRCC.

The genome of the deep-sea anemone Actinernus sp. contains a mega-array of ANTP-class homeobox genes.

Members of the phylum Cnidaria include sea anemones, corals and jellyfish, and have successfully colonized both marine and freshwater habitats throughout the world. The understanding of how cnidarians adapt to extreme environments such as the dark, high-pressure deep-sea habitat has been hindered by the lack of genomic information. Here, we report the first chromosome-level deep-sea cnidarian genome, of the anemone Actinernus sp., which was 1.39 Gbp in length and contained 44 970 gene models including 14 806 tRNA genes and 30 164 protein-coding genes. Analyses of homeobox genes revealed the longest chromosome hosts a mega-array of Hox cluster, HoxL, NK cluster and NKL homeobox genes; until now, such an array has only been hypothesized to have existed in ancient ancestral genomes. In addition to this striking arrangement of homeobox genes, analyses of microRNAs revealed cnidarian-specific complements that are distinctive for nested clades of these animals, presumably reflecting the progressive evolution of the gene regulatory networks in which they are embedded. Also, compared with other sea anemones, circadian rhythm genes were lost in Actinernus sp., which likely reflects adaptation to living in the dark. This high-quality genome of a deep-sea cnidarian thus reveals some of the likely molecular adaptations of this ecologically important group of metazoans to the extreme deep-sea environment. It also deepens our understanding of the evolution of genome content and organization of animals in general and cnidarians in particular, specifically from the viewpoint of key developmental control genes like the homeobox-encoding genes, where we find an array of genes that until now has only been hypothesized to have existed in the ancient ancestor that pre-dated both the cnidarians and bilaterians.

Discovery of Novel Bruton's Tyrosine Kinase PROTACs with Enhanced Selectivity and Cellular Efficacy.

Bruton's tyrosine kinase (BTK) is a target for treating B-cell malignancies and autoimmune diseases, and several BTK inhibitors are already approved for use in humans. Heterobivalent BTK protein degraders are also in development, based on the premise that proteolysis targeting chimeras (PROTACs) may provide additional therapeutic benefits. However, most BTK PROTACs are based on the BTK inhibitor ibrutinib raising concerns about their selectivity profiles, given the known off-target effects of ibrutinib. Here, we disclose the discovery and in vitro characterization of BTK PROTACs based on the selective BTK inhibitor GDC-0853 and the cereblon recruitment ligand pomalidomide. PTD10 is a highly potent BTK degrader (DC50 0.5 nM) that inhibited cell growth and induced apoptosis at lower concentrations than the two parent molecules, as well as three previously reported BTK PROTACs, and had improved selectivity compared to ibrutinib-based BTK PROTACs.

A molecular networking-based isolation of gardneria alkaloids from Gardneria distincta and their anti-inflammatory activity.

Gardneria distincta P. T. Li is traditionally applied as a herbal medicine for treatment various ailments, and is mainly distributed in Southwestern China. Under the guided separation of MS/MS-based molecular networking, eight undescribed oxindole alkaloids, gardistines A-H, as well as 17 known alkaloids were discovered from the whole parts of Gardneria distincta. Structural elucidation of these undescribed alkaloids was performed by various spectroscopic methods. Gardistine A is a rare oxindole gardneria alkaloid bearing an ester carbonyl group attached to C-18, which is the second reported alkaloid of oxindole gardneria-type. All of the identified monoterpene indole alkaloids were investigated for their anti-inflammatory activity in LPS-induced RAW 264.7 cells. Gardistines A-B and akuammidine demonstrated significant inhibitory effects on the expressions of nitric oxide, tumor necrosis factor alpha, and interleukin-6 at 20 µM.

Structural variation (SV)-based pan-genome and GWAS reveal the impacts of SVs on the speciation and diversification of allotetraploid cottons.

Structural variations (SVs) have long been described as being involved in the origin, adaption, and domestication of species. However, the underlying genetic and genomic mechanisms are poorly understood. Here, we report a high-quality genome assembly of Gossypium barbadense acc. Tanguis, a landrace that is closely related to formation of extra-long-staple (ELS) cultivated cotton. An SV-based pan-genome (Pan-SV) was then constructed using a total of 182 593 non-redundant SVs, including 2236 inversions, 97 398 insertions, and 82 959 deletions from 11 assembled genomes of allopolyploid cotton. The utility of this Pan-SV was then demonstrated through population structure analysis and genome-wide association studies (GWASs). Using segregation mapping populations produced through crossing ELS cotton and the landrace along with an SV-based GWAS, certain SVs responsible for speciation, domestication, and improvement in tetraploid cottons were identified. Importantly, some of the SVs presently identified as associated with the yield and fiber quality improvement had not been identified in previous SNP-based GWAS. In particular, a 9-bp insertion or deletion was found to associate with elimination of the interspecific reproductive isolation between Gossypium hirsutum and G. barbadense. Collectively, this study provides new insights into genome-wide, gene-scale SVs linked to important agronomic traits in a major crop species and highlights the importance of SVs during the speciation, domestication, and improvement of cultivated crop species.

Small RNAs in Cnidaria: A review.

As fundamental components of RNA silencing, small RNA (sRNA) molecules ranging from 20 to 32 nucleotides in length have been found as potent regulators of gene expression and genome stability in many biological processes of eukaryotes. Three major small RNAs are active in animals, including the microRNA (miRNA), short interfering RNA (siRNA), and PIWI-interacting RNA (piRNA). Cnidarians, the sister group to bilaterians, are at a critical phylogenetic node to better model eukaryotic small RNA pathway evolution. To date, most of our understanding of sRNA regulation and its potential contribution to evolution has been limited to a few triploblastic bilaterian and plant models. The diploblastic nonbilaterians, including the cnidarians, are understudied in this regard. Therefore, this review will present the current-known small RNA information in cnidarians to enhance our understanding of the development of the small RNA pathways in early branch animals.

Genomic insights into the genetic basis of cotton breeding in China.

The excellent Upland cotton (Gossypium hirsutum) cultivars developed since 1949 have made a huge contribution to cotton production in China, the world's largest producer and consumer of cotton. However, the genetic and genomic basis for the improvements of these cotton cultivars remains largely unclear. In this study, we selected 16 Upland cotton cultivars with important historical status in Chinese cotton breeding and constructed a multiparent, advanced generation, intercross (MAGIC) population comprising 920 recombinant inbred lines. A genome-wide association study using the MAGIC population identified 54 genomic loci associated with lint yield and fiber quality. Of them, 25 (46.30%) pleiotropic genomic loci cause simultaneous changes of lint yield and/or fiber quality traits, revealing complex trade-offs and linkage drags in Upland cotton agronomic traits. Deep sequencing data of 11 introduced ancestor cultivars and publicly available resequencing datasets of 839 cultivars developed in China during the past 70 years were integrated to explore the historical distribution and origin of the elite or selected alleles. Interestingly, 85% of these elite alleles were selected and fixed from different American ancestors, consistent with cotton breeding practices in China. However, seven elite alleles of native origin that are responsible for Fusarium wilt resistance, early maturing, good-quality fiber, and other characteristics were not found in American ancestors but have greatly contributed to Chinese cotton breeding and wide cultivation. Taken together, these results provide a genetic basis for further improving cotton cultivars and reveal that the genetic composition of Chinese cotton cultivars is narrow and mainly derived from early introduced American varieties.

Lathyrol promotes ER stress-induced apoptosis and proliferation inhibition in lung cancer cells by targeting SERCA2.

Lathyrol is a natural product isolated from the traditional Chinese medicine Semen Euphorbiae with unknown anti-tumor effects. We found that lathyrol had significant inhibitory effect on lung cancer cells by inducing apoptosis and inhibiting proliferation. Subsequently, we demonstrated for the first time that endoplasmic reticulum (ER) stress is a key anti-tumor mechanism of lathyrol. Furthermore, we found that lathyrol can induce ER stress in lung cancer cells by upregulating the protein expression levels of GRP78, PERK, p-eIF2α, CHOP, and ATF4, and the inhibitory effect of lathyrol on lung cancer cells was significantly reversed when cells were pretreated with ER stress inhibitor. In addition, we found that inhibition of SERCA2 resulted in depletion of the ER Ca2+ pool followed by a sustained increase in cytoplasmic Ca2+ levels, eventually leading to ER stress induced tumor cell apoptosis and proliferation inhibition. Lathyrol targeted SERCA2 to cause a significant upregulation of Ca2+ levels, and the inhibitory effect of lathyrol on lung cancer cells was significantly reversed after pretreatment with SERCA2 agonist. Taken together, our data suggest that lathyrol exerts its anti-tumor effect primarily by targeting SERCA2. Our findings highlight the potential for lathyrol as a new candidate drug for the treatment of lung cancer.

The Effect of Plasma on Bacteria and Normal Cells in Infected Wound.

Infected wound is one of the most common and serious problem in wound management. Cold atmospheric plasma (CAP) is considered to have a good effect in wound healing as a new type medicine. However, there is a key issue that has not been addressed in the treatment of infected wounds by plasma. Bacteria are always found in the deep region of the wound. When plasma is used to treat wounds, it also acts on normal tissue cells while decontaminating. What is the difference between the same dose of plasma acting on bacteria and normal cells? In this study, the most common bacteria (S. aureus, P. aeruginosa, and E. coli) in infected wound and two kinds of normal skin cells (human keratinocyte and human skin fibroblasts (HSF)) were selected to study the difference of the effects of the same dose of plasma on bacteria and cells. The results reveal that three kinds of 106 CFU mL bacteria could be effectively inactivated by 5 order after plasma treatment 3 min, and P. aeruginosa was more sensitive to plasma (could be inactivated 5 order after 2 min treatment). The 104 mL keratinocyte and HSF were treated with the same dose of plasma; keratinocyte can maintain over 90% of the activity and HSF cells can maintain over 70% of the activity. Moreover, the level of collagen I secreted by HSF increased. Therefore, cells can remain a high activity when a plasma dose capable of inactivating bacteria is applied to them.

Identification and differential analysis of noncoding RNAs in response to drought in Phyllostachys aureosulcata f. spectabilis.

The role of noncoding RNAs (ncRNAs) in plant resistance to abiotic stresses is increasingly being discovered. Drought stress is one of the most common stresses that affecting plant growth, and high intensity drought has a significant impact on the normal growth of plants. In this study, a high-throughput sequencing was performed on plant tissue samples of Phyllostachys aureosulcata f. spectabilis C. D. Chu et C. S. Chao by drought treatment for 0, 2, 4 and 6 days. The sequencing results were analysed bioinformatically. We detected 336,946 RNAs among all 12 samples, including 192,098 message RNAs (mRNAs), 142,761 long noncoding RNAs (lncRNAs), 1,670 circular RNAs (circRNAs), and 417 microRNAs (miRNAs). We detected 2,419 differentially expressed (DE) ncRNAs, including 213 DE circRNAs, 2,088 DE lncRNAs and 118 DE miRNAs. Then, we used Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to functionally predict DE ncRNAs. The results showed that most DE ncRNAs are involved in the response to drought stress, mainly in biochemical reactions involved in some metabolites, as well as in organelle activities. In addition, we validated two random circRNAs and demonstrated their circularity. We also found a stable internal reference gene available for Phyllostachys aureosulcata f. spectabilis and validated the accuracy of this experiment by quantitative real-time polymerase chain reaction (qRT-PCR).

Identification of elite fiber quality loci in upland cotton based on the genotyping-by-target-sequencing technology.

Genome-wide association studies (GWAS) of fiber quality traits of upland cotton were conducted to identify the single-nucleotide polymorphic (SNP) loci associated with cotton fiber quality, which lays the foundation for the mining of elite] cotton fiber gene resources and its application in molecular breeding. A total of 612 upland cotton accessions were genotyped using the ZJU Cotton Chip No. 1 40K chip array via the liquid-phase probe hybridization-based genotyping-by-target-sequencing (GBTS) technology. In the present study, five fiber quality traits, namely fiber length, fiber strength, micronaire, uniformity and elongation, showed different degrees of variation in different environments. The average coefficient of variation of fiber strength was the greatest, whereas the average coefficient of variation of uniformity was the least. Significant or extremely significant correlations existed among the five fiber quality traits, especially fiber length, strength, uniformity and elongation all being significantly negative correlated with micronaire. Population cluster analysis divided the 612 accessions into four groups: 73 assigned to group I, 226 to group II, 220 to group III and 93 to group IV. Genome-wide association studies of five fiber quality traits in five environments was performed and a total of 42 SNP loci associated with target traits was detected, distributed on 19 chromosomes, with eight loci associated with fiber length, five loci associated with fiber strength, four loci associated with micronaire, twelve loci associated with fiber uniformity and thirteen loci associated with fiber elongation. Of them, seven loci were detected in more than two environments. Nine SNP loci related to fiber length, fiber strength, uniformity and elongation were found on chromosome A07, seven loci related to fiber length, fiber strength, micronaire and elongation were detected on chromosome D01, and five loci associated with fiber length, uniformity and micronaire were detected on chromosome D11. The results from this study could provide more precise molecular markers and genetic resources for cotton breeding for better fiber quality in the future.

Solid-solution reaction suppresses the Jahn-Teller effect of potassium manganese hexacyanoferrate in potassium-ion batteries.

Potassium manganese hexacyanoferrate (KMnHCF) suffers from poor cycling stability in potassium-ion batteries due to the Jahn-Teller effect, and experiences destabilizing asymmetric expansions and contractions during cycling. Herein, hollow nanospheres consisting of ultrasmall KMnHCF nanocube subunits (KMnHCF-S) are developed by a facile strategy. In situ XRD analysis demonstrates that the traditional phase transition for KMnHCF is replaced by a single-phase solid-solution reaction for KMnHCF-S, which effectively suppresses the Jahn-Teller effect. From DFT calculations, it was found that the calculated reaction energy for K+ extraction in the solid-solution reaction is much lower than that in the phase transition, indicating easier K+ extraction during the solid-solution reaction. KMnHCF-S delivers high capacity, outstanding rate capability, and superior cycling performance. Impressively, the K-ion full cell composed of the KMnHCF-S cathode and graphite anode also displays excellent cycling stability. The solid-solution reaction not only suppresses the Jahn-Teller effect of KMnHCF-S but also provides a strategy to enhance the electrochemical performance of other electrodes which undergo phase transitions.

Salinomycin suppresses T24 cells by regulating KDM1A and the unfolded protein response pathway.

In recent years, salinomycin has been shown to exert an anticancer effect in a variety of tumors; however, its function and mechanism in bladder cancer (BC) remain unclear. This study examined the effect of salinomycin on bladder cancer and analyzed its regulatory mechanism. T24 cells were treated with different concentrations of salinomycin to detect subsequent changes in cell proliferation, apoptosis, oxidative stress, H3K4 methylation, and related gene expression by the CCK8 assay, Edu staining, Tunel staining, ELISA, RT-qPCR, and western blotting, respectively. A KDM1A overexpression plasmid, catalytically inactive KDM1A overexpression plasmid, or short hairpin RNA (shRNA) plasmid was transfected into T24 cells to evaluate their effects. A xenograft tumor model was used to further confirm the anti-tumor effect of salinomycin. Our results showed that salinomycin significantly inhibited cell proliferation, promoted apoptosis, increased MDA levels, decreased SOD levels, induced H3K4 histone methylation, and suppressed KDM1A expression. Furthermore, the sh-KDM1A plasmid had effects similar to those of salinomycin and also activated the unfolded protein response pathway. The KDM1A overexpression plasmid had effects opposite to those of the sh-KDM1A plasmid, and the catalytically inactive KDM1A overexpression plasmid had no effect. Meanwhile, KDM1A overexpression reversed the effects of salinomycin on T24 cells. Finally, in vivo experiments confirmed the above results. In the salinomycin treatment group, tumor growth and KDM1A expression were suppressed and cell apoptosis and UPR were induced, while treatment with the KDM1A overexpression plasmid produced the opposite effects. Collectively, our study revealed that salinomycin suppressed T24 cell proliferation and promoted oxidative stress and apoptosis by regulating KDM1A and the UPR pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-022-00546-y.

Genome of the sea anemone Exaiptasia pallida and transcriptome profiles during tentacle regeneration.

Cnidarians including sea anemones, corals, hydra, and jellyfishes are a group of animals well known for their regeneration capacity. However, how non-coding RNAs such as microRNAs (also known as miRNAs) contribute to cnidarian tissue regeneration is poorly understood. Here, we sequenced and assembled the genome of the sea anemone Exaiptasia pallida collected in Hong Kong waters. The assembled genome size of E. pallida is 229.21 Mb with a scaffold N50 of 10.58 Mb and BUSCO completeness of 91.1%, representing a significantly improved genome assembly of this species. The organization of ANTP-class homeobox genes in this anthozoan further supported the previous findings in jellyfishes, where most of these genes are mainly located on three scaffolds. Tentacles of E. pallida were excised, and both mRNA and miRNA were sequenced at 9 time points (0 h, 6 h, 12 h, 18 h, 1 day, 2, 3, 6, and 8 days) from regenerating tentacles. In addition to the Wnt signaling pathway and homeobox genes that are shown to be likely involved in tissue regeneration as in other cnidarians, we have shown that GLWamide neuropeptides, and for the first time sesquiterpenoid pathway genes could potentially be involved in the late phase of cnidarian tissue regeneration. The established sea anemone model will be useful for further investigation of biology and evolution in, and the effect of climate change on this important group of animals.

New Frontier in Antiviral Drugs for Disorders of the Respiratory System.

BACKGROUND: COVID-19 is still soaring, and the new delta COVID-19 variant is on the rise and spreading around the world. OBJECTIVE: We conducted a patent analysis to better understand the therapeutic strategy developed for antivirals available for the disorders of the respiratory system. MATERIALS AND METHODS: European granted patents filed from January 2002 to June 2021 were analyzed. We used a combination of International patent classification (IPC) "A61p31/12" and "A61p11/00" to search the relevant documents. RESULTS: Our study showed R&D of antiviral drugs for disorders of the respiratory system to be decreasing over the past 20 years. Chemical drugs showed various chemical structures. The development of chemical drugs or herbal medicines appeared to commence earlier than the biological products. Also, the results indicated that large global companies play a leading role in developing kinase inhibitors as chemical drugs. CONCLUSION: There are three strategies for developing antiviral drugs for the disorders of the respiratory system, including chemical drugs, herbal medicines or natural products, and biological products. Herbal medicines may provide a new insight and approach to developing antiviral drugs for disorders of the respiratory system. A combination of chemical drugs and natural products may be a promising therapeutic method for treating patients with COVID- 19.

Genome of the ramshorn snail Biomphalaria straminea-an obligate intermediate host of schistosomiasis.

BACKGROUND: Schistosomiasis, or bilharzia, is a parasitic disease caused by trematode flatworms of the genus Schistosoma. Infection by Schistosoma mansoni in humans results when cercariae emerge into water from freshwater snails in the genus Biomphalaria and seek out and penetrate human skin. The snail Biomphalaria straminea is native to South America and is now also present in Central America and China, and represents a potential vector host for spreading schistosomiasis. To date, genomic information for the genus is restricted to the neotropical species Biomphalaria glabrata. This limits understanding of the biology and management of other schistosomiasis vectors, such as B. straminea. FINDINGS: Using a combination of Illumina short-read, 10X Genomics linked-read, and Hi-C sequencing data, our 1.005 Gb B. straminea genome assembly is of high contiguity, with a scaffold N50 of 25.3 Mb. Transcriptomes from adults were also obtained. Developmental homeobox genes, hormonal genes, and stress-response genes were identified, and repeat content was annotated (40.68% of genomic content). Comparisons with other mollusc genomes (including Gastropoda, Bivalvia, and Cephalopoda) revealed syntenic conservation, patterns of homeobox gene linkage indicative of evolutionary changes to gene clusters, expansion of heat shock protein genes, and the presence of sesquiterpenoid and cholesterol metabolic pathway genes in Gastropoda. In addition, hormone treatment together with RT-qPCR assay reveal a sesquiterpenoid hormone responsive system in B. straminea, illustrating that this renowned insect hormonal system is also present in the lophotrochozoan lineage. CONCLUSION: This study provides the first genome assembly for the snail B. straminea and offers an unprecedented opportunity to address a variety of phenomena related to snail vectors of schistosomiasis, as well as evolutionary and genomics questions related to molluscs more widely.

Recent Trend for EGFR-Based and ALK-Based Targets: A Patent Analysis.

BACKGROUND: Epidermal growth factor receptor and anaplastic lymphoma kinase play key roles in tumorigenesis and disease progression. Currently, targeted therapy is a better approach for cancer therapy compared with traditional chemotherapy. EGFR-based/ALK-based target therapies are key targets for drug development in cancer therapy. OBJECTIVE: The objective of this study was to show a recent trend in research and development of EGFR-based/ALK-based targets and to better understand the Intellectual Property surrounding EGFR-based and ALK-based targets. METHODS: EGFR-based and ALK-based targets were analyzed by comprehensive US patent analysis. US patents of EGFR-based/ALK-based targets were analyzed from September 2001 to September 2020. RESULTS: The results indicated that the key technologies and methods of EGFR-based/ALK-based targets were developed by large global pharmaceutical companies or American companies/universities. Small molecular inhibitors showed a higher percentage in the number of patents of EGFRbased targets. In addition, the present study also showed recent small molecular targeted drugs approved by FDA. CONCLUSION: Global large pharmaceutical companies and American companies/universities have obvious advantages in the research and development of targeted drugs. EGFR-based target was still an attractive target for research and drug development in the past 10 years. Also, large global pharmaceutical companies prefer to complete key technology research and development by independent innovation instead of collaboration.