Overcoming the High Error Rate of Composite DNA Letters-Based Digital Storage through Soft-Decision Decoding.

Composite DNA letters, by merging all four DNA nucleotides in specified ratios, offer a pathway to substantially increase the logical density of DNA digital storage (DDS) systems. However, these letters are susceptible to nucleotide errors and sampling bias, leading to a high letter error rate, which complicates precise data retrieval and augments reading expenses. To address this, Derrick-cp is introduced as an innovative soft-decision decoding algorithm tailored for DDS utilizing composite letters. Derrick-cp capitalizes on the distinctive error sensitivities among letters to accurately predict and rectify letter errors, thus enhancing the error-correcting performance of Reed-Solomon codes beyond traditional hard-decision decoding limits. Through comparative analyses in the existing dataset and simulated experiments, Derrick-cp's superiority is validated, notably halving the sequencing depth requirement and slashing costs by up to 22% against conventional hard-decision strategies. This advancement signals Derrick-cp's significant role in elevating both the precision and cost-efficiency of composite letter-based DDS.

Improving error-correcting capability in DNA digital storage via soft-decision decoding.

Error-correcting codes (ECCs) employed in the state-of-the-art DNA digital storage (DDS) systems suffer from a trade-off between error-correcting capability and the proportion of redundancy. To address this issue, in this study, we introduce soft-decision decoding approach into DDS by proposing a DNA-specific error prediction model and a series of novel strategies. We demonstrate the effectiveness of our approach through a proof-of-concept DDS system based on Reed-Solomon (RS) code, named as Derrick. Derrick shows significant improvement in error-correcting capability without involving additional redundancy in both in vitro and in silico experiments, using various sequencing technologies such as Illumina, PacBio and Oxford Nanopore Technology (ONT). Notably, in vitro experiments using ONT sequencing at a depth of 7× reveal that Derrick, compared with the traditional hard-decision decoding strategy, doubles the error-correcting capability of RS code, decreases the proportion of matrices with decoding-failure by 229-fold, and amplifies the potential maximum storage volume by impressive 32 388-fold. Also, Derrick surpasses 'state-of-the-art' DDS systems by comprehensively considering the information density and the minimum sequencing depth required for complete information recovery. Crucially, the soft-decision decoding strategy and key steps of Derrick are generalizable to other ECCs' decoding algorithms.

Deciphering the Plastomic Code of Chinese Hog-Peanut (Amphicarpaea edgeworthii Benth., Leguminosae): Comparative Genomics and Evolutionary Insights within the Phaseoleae Tribe.

The classification and phylogenetic relationships within the Phaseoleae tribe (Leguminosae) have consistently posed challenges to botanists. This study addresses these taxonomic intricacies, with a specific focus on the Glycininae subtribe, by conducting a comprehensive analysis of the highly conserved plastome in Amphicarpaea edgeworthii Benth., a critical species within this subtribe. Through meticulous genomic sequencing, we identified a plastome size of 148,650 bp, composed of 128 genes, including 84 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. Comparative genomic analysis across seven Glycininae species illuminated a universally conserved circular and quadripartite structure, with nine genes exhibiting notable nucleotide diversity, signifying a remarkable genomic variability. Phylogenetic reconstruction of 35 Phaseoleae species underscores the affinity of Amphicarpaea with Glycine, placing Apios as a sister lineage to all other Phaseoleae species, excluding Clitorinae and Diocleinae subtribes. Intriguingly, Apios, Butea, Erythrina, and Spatholobus, traditionally clumped together in the Erythrininae subtribe, display paraphyletic divergence, thereby contesting their taxonomic coherence. The pronounced structural differences in the quadripartite boundary genes among taxa with unresolved subtribal affiliations demand a reevaluation of Erythrininae's taxonomic classification, potentially refining the phylogenetic contours of the tribe.

Protective effect of quercetin on cadmium-induced kidney apoptosis in rats based on PERK signaling pathway.

BACKGROUND: Cadmium (Cd) is a highly toxic environmental pollutant that can enter the body through bioaccumulation. The kidney is an important target organ for Cd poisoning. Quercetin (Que) is a natural flavonoid compound with free radical scavenging and antioxidant properties. Previous studies showed that Que can alleviate kidney damage caused by Cd poisoning in rats, but the specific mechanism is still unclear. METHODS: Twenty-four male Sprague-Dawley (SD) rats were divided into four groups: normal saline-treated control group, Cd group treated by intraperitoneal injection of 2 mg/kg b.w. CdCl2, Cd + Que group treated by intraperitoneal injection of 2 mg/kg b.w. CdCl2 and 100 mg/kg b.w. Que, and Que group treated by 100 mg/kg b.w. Que. Four weeks later, the rats were anesthetized with diethyl ether, and blood was taken intravenously. The rats were executed with their necks cut off, and the kidneys were removed. Body weight, kidney organ weight, and glutathione (GSH) and malondialdehyde (MDA) levels were measured. The structure of kidney tissue was observed by hematoxylin and eosin staining, kidney cell apoptosis was detected by TUNEL assay, and the mRNA expression levels of genes related to the PERK signaling pathway were analyzed by RT-PCR. RESULTS: Compared with the control group, the Cd-treated group exhibited a significant decrease in body weight (P < 0.01). Their kidneys showed a significant increase in the relative organ weight (P < 0.01). Moreover, the MDA and GSH levels increased. Kidney tissue damage and renal cell apoptosis were observed, and the mRNA expression levels of genes related to the PERK signaling pathway significantly increased (P < 0.01). Compared with the Cd-treated group, the Cd + Que group exhibited a significant increase in body weight (P < 0.01) and significant decreases in the relative organ weight, MDA and GSH levels, and mRNA expression levels of genes related to the PERK signaling pathway (P < 0.01). Furthermore, kidney tissue damage and renal cell apoptosis were observed. CONCLUSION: Cd treatment resulted in rat weight loss, renal edema, and oxidative stress and caused renal tissue damage and cell apoptosis by activating the PERK signaling pathway. Que was able to restore the body weight and renal coefficient of rats. It also alleviated the oxidative stress and kidney tissue damage caused by Cd and the cell apoptosis caused by Cd through inhibiting the PERK signaling pathway. Thus, Que could be considered for the treatment of kidney diseases caused by Cd poisoning.

A Review on the Morphology, Cultivation, Identification, Phytochemistry, and Pharmacology of Kitagawia praeruptora (Dunn) Pimenov.

Kitagawia praeruptora (Dunn) Pimenov, commonly known as Qianhu in China, is a widely used folk Chinese herbal medicine. This article reviews its botanical traits, ethnopharmacology, cultivation techniques, identification, phytochemical compositions, and pharmacological effects. Over 70 coumarin compounds, including simple coumarins, pyranocoumarins, and furanocoumarins, have been isolated within this plant. Additionally, K. praeruptora contains other components such as flavonoids, fatty acids, benzoic acids, and sterols. This information highlights the importance of utilizing active ingredients and excavating pharmacological effects. With its remarkable versatility, K. praeruptora exhibits a wide range of pharmacological effects. It has been found to possess expectorant and bronchodilator properties, cardiovascular protection, antimicrobial and antioxidant activities, anti-tumor effects, and even antidiabetic properties. It is recommended to focus on the development of new drugs that leverage the active ingredients of K. praeruptora and explore its potential for new clinical applications and holistic utilization.

Quercetin alleviates cadmium-induced BRL-3A cell apoptosis by inhibiting oxidative stress and the PERK/IRE1α/ATF6 signaling pathway.

Cadmium (Cd) is a highly toxic environmental pollutant. The liver is an important metabolic organ in the body and is susceptible to Cd toxicity attacks. Quercetin (Que) is a flavonoid compound with pharmacological activities of scavenging free radicals and antioxidant activity. Previous studies have shown that Que can alleviate Cd caused hepatocyte apoptosis in rats, but the specific mechanism remains unclear. To explore the specific mechanism, we established a model of Cd toxicity and Que rescue in BRL-3A cells and used 4-phenylbutyrate (4-PBA), an endoplasmic reticulum stress (ERS) inhibitor, as positive control. Set up a control group, Cd treatment group, Cd and Que co treatment group, Que treatment group, Cd and 4-PBA co treatment group, and 4-PBA treatment group. Cell Counting Kit-8 (CCK-8) method was employed to measure cell viability. Fluorescence staining was applied to observe cell apoptosis. Flow cytometry was performed to detect reactive oxygen species levels. Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot method was adopted to detect the mRNA and protein expression levels of ERS and apoptosis-related genes. The results showed that compared with the control group, the Cd treated group showed a significant decrease in cell viability (P < 0.01), an increase in intracellular ROS levels, and apoptosis. The mRNA and protein expression levels of ERS and apoptosis related factors such as GRP78, IRE1α, XBP1, ATF6, Caspase-12, Caspase-3 and Bax in the cells were significantly increased (P < 0.01), while the mRNA and protein expression levels of Bcl-2 were significantly reduced (P < 0.01). Compared with the Cd treatment group, the Cd and Que co treatment group and the Cd and 4-PBA co treatment group showed a significant increase in cell viability (P < 0.01), a decrease in intracellular ROS levels, a decrease in cell apoptosis, and a significant decrease in the expression levels of ERS and apoptosis related factors mRNA and protein (P < 0.01), as well as a significant increase in Bcl-2 mRNA and protein expression (P < 0.01). We confirmed that Que could alleviate the apoptosis caused by Cd in BRL-3A cells, and the effects of Que were similar to those of ERS inhibitor.

Acting on ethics and governance of aging research.

Rapid advances in aging research and clinical translation come with numerous ethical and societal issues that the current regulatory framework may not be sufficient to address. To fill this gap, we propose a responsible and comprehensive governance framework to cope with these issues while maximizing the benefits of aging research.

Protective effect of quercetin on cadmium-induced renal apoptosis through cyt-c/caspase-9/caspase-3 signaling pathway.

Cadmium (Cd), a heavy metal, has harmful effects on animal and human health, and it can also obviously induce cell apoptosis. Quercetin (Que) is a flavonoid compound with antioxidant and other biological activities. To investigate the protective effect of Que on Cd-induced renal apoptosis in rats. 24 male SD rats were randomly divided into four groups. They were treated as follows: control group was administered orally with normal saline (10 ml/kg); Cd group was injected with 2 mg/kg CdCl2 intraperitoneally; Cd + Que group was injected with 2 mg/kg CdCl2 and intragastric administration of Que (100 mg/kg); Que group was administered orally with Que (100 mg/kg). The experimental results showed that the body weight of Cd-exposed rats significantly decreased and the kidney coefficient increased. In addition, Cd significantly increased the contents of Blood Urea Nitrogen, Creatinine and Uric acid. Cd also increased the glutathione and malondialdehyde contents in renal tissues. The pathological section showed that Cd can cause pathological damages such as narrow lumen and renal interstitial congestion. Cd-induced apoptosis of kidney, which could activate the mRNA and protein expression levels of Cyt-c, Caspase-9 and Caspase-3 were significantly increased. Conversely, Que significantly reduces kidney damage caused by Cd. Kidney pathological damage was alleviated by Que. Que inhibited Cd-induced apoptosis and decreased Cyt-c, Caspase-9 and Caspase-3 proteins and mRNA expression levels. To sum up, Cd can induce kidney injury and apoptosis of renal cells, while Que can reduce Cd-induced kidney damage by reducing oxidative stress and inhibiting apoptosis. These results provide a theoretical basis for the clinical application of Que in the prevention and treatment of cadmium poisoning.

Alleviating effect of quercetin on cadmium-induced oxidative damage and apoptosis by activating the Nrf2-keap1 pathway in BRL-3A cells.

Cadmium (Cd) is a toxic heavy metal extensively used in industrial and agricultural production. Among the main mechanisms of Cd-induced liver damage is oxidative stress. Quercetin (QE) is a natural antioxidant. Herein, the protective effect of QE on Cd-induced hepatocyte injury was investigated. BRL-3A cells were treated with 12.5 µmol/L CdCl2 and/or 5 µmol/L QE for 24 h. The cells and medium supernatant were collected, and the ALT, AST, and LDH contents of the medium supernatant were detected. The activities or contents of SOD, CAT, GSH, and MDA in cells were determined. Intracellular ROS levels were examined by flow cytometry. Apoptosis rate and mitochondrial-membrane potential (ΔΨm) were detected by Hoechst 33,258 and JC-1 methods, respectively. The mRNA and protein expression levels of Nrf2, NQO1, Keap1, CytC, caspase-9, caspase-3, Bax, and Bcl-2 were determined by real-time PCR (RT-PCR) and Western blot methods. Results showed that Cd exposure injured BRL-3A cells, the activity of antioxidant enzymes decreased and the cell ROS level increased, whereas the ΔΨm decreased, and the expression of apoptotic genes increased. Cd inhibited the Nrf2-Keap1 pathway, decreased Nrf2 and NQO1, or increased Keap1 mRNA and protein expression. Through the combined action of Cd and QE, QE activated the Nrf2-Keap1 pathway. Consequently, antioxidant-enzyme activity decreased, cellular ROS level decreased, ΔΨm increased, Cd-induced BRL-3A cell damage was alleviated, and cell apoptosis was inhibited. After the combined action of QE and Cd, Nrf2 and NQO1 mRNA and protein expression increased, Keap1 mRNA and protein expression decreased. Therefore, QE exerted an antioxidant effect by activating the Nrf2-Keap1 pathway in BRL-3A cells.

Role of endoplasmic reticulum stress in cadmium-induced hepatocyte apoptosis and the protective effect of quercetin.

Cadmium (Cd) is one of the most toxic environmental pollutants. Quercetin (Que) is a kind of natural flavonoid with neuroprotective, antioxidant, and free-radical scavenging pharmacological activities. However, whether Que has the protective effect of on Cd-induced rat hepatocyte injury is unclear. This study aimed to determine the protective effect of Que on Cd-induced hepatotoxicity in vivo and in vitro. For in vivo, 36 4-week-old male SD rats were randomly divided into six groups and were treated with CdCl2 (2 mg/kg b.w.) and/or Que (50 or 100 mg/kg b.w.). Four weeks later, the rats were sacrificed and livers were collected. The levels of alanine aminotransferase, aspartate aminotransferase, glutathione, malondialdehyde, catalase, and superoxide dismutase were measured. Liver histopathological sections were made, and TUNEL method was performed to detect cell apoptosis. The mRNA and protein expression levels of endoplasmic reticulum stress (ERS) signaling pathway-related factors and apoptosis-related factors were detected. For in vitro, BRL-3A rat cells were treated with CdCl2 (12.5 µM) and/or Que (5 µM Que). The mRNA and protein expression levels of ERS signaling pathway-related factors and apoptosis-related factors were detected. Results showed that Cd led to liver injury, disorder of hepatocyte morphology and structure, decreased BRL-3A cells viabilities, increased oxidative damage. The mRNA and protein expression levels of ERS related factors GRP78, PERK, eIF2α, ATF4, CHOP, IRE1α, XBP1, and ATF6 increased. The mRNA and protein levels of apoptosis related factors Caspase12, Caspase3, and Bax increased, whereas Bcl2 decreased. It indicated that cadmium could activate PERK-eIF2α-ATF4-CHOP, IRE1α-XBP1, and ATF6-CHOP ERS-related signal pathways and lead to apoptosis. Moreover, Que can improve the vitality of hepatocytes, and effectively reduce hepatocytes damage, and reduce oxidative damage by Cd. As a result, the mRNA and protein expression levels of ERS related factors were reduced and hepatocyte apoptosis related factors decreased. Therefore, Que can be used as an effective component in daily diet to prevent Cd toxicity.

Knowledge graphs of ethical concerns of cerebral organoids.

OBJECTIVES: The rapid development of cerebral organoid technology and the gradual maturity of cerebral organoids highlight the necessity of foresighted research on relevant ethical concerns. We employed knowledge graphs and conducted statistical analysis with CiteSpace for a comprehensive analysis of the status quo of the research on the ethical concerns of cerebral organoids from a bibliometric perspective. MATERIALS AND METHODS: We performed a statistical analysis of published papers on cerebral organoid ethics, keyword co-occurrence graph, literature co-citation and knowledge clustering graph to examine the status of the ethics research, internal relationship between technological development and ethical research, and ethical concerns of the academia. Finally, we used a keyword time zone graph and related statistics to analyze and predict the trends and popular topics of future cerebral organoids ethics research. RESULTS: We demonstrated that although the ethical concerns of cerebral organoids have long been discussed, it was not until 2017 that the ethical issues began to receive more attention, when cerebral organoids were gradually mimicking the human brain more closely and increasingly being combined with chimera research. The recent key ethical concerns are primarily divided into three categories: concerns that are common in life sciences, specific to cerebral organoids, and present in cross-fields. These increasing ethical concerns are inherently related to the continual development of technology. The analysis pointed out that future research should focus on the ethical concerns of consciousness that are unique to cerebral organoids, ethical concerns of cross-fields, and construction and improvement of legislative and regulatory systems. CONCLUSIONS: Although research on cerebral organoids can benefit the biomedicine field, the relevant ethical concerns are significant and have received increasing attention, which are inherently related to the continual development of technology. Future studies in ethics regarding cerebral organoid research should focus on the ethical concerns of consciousness, and cross-fields, as well as the improvement of regulatory systems.

Responsible governance of human germline genome editing in China†.

Considerable improvements have been made to gene editing technology, which has been increasingly applied to research involving humans. Nevertheless, human heritable germline genome editing is associated with a series of potential ethical, legal, and social risks, which have generated major controversies and discussions worldwide, especially after the "gene-edited babies" incident. Influenced by this incident, China has realized the importance of ethical governance in the field of life science and technology, has accelerated legislative and policy efforts in this field, and has gradually moved toward the direction of "precautionary" ethical governance. Black letter analysis, big data public opinion analysis, and other research methods are used in this paper. This paper explores the scientific background, ethical debates, and latest developments regarding China's regulatory framework for human germline gene editing after the "gene-edited babies" controversy and provides several recommendations on the future governance system of human germline gene editing in China. This paper argues that in recent years, the ethics governance of germline genome editing in China has been accelerated and great changes have been made. However, the regulatory system for germline genome editing requires further improvement in three aspects: coordination of legislation and agencies, establishment of an ethics review system at high levels, and public participation and education.

A highly stable human single-domain antibody-drug conjugate exhibits superior penetration and treatment of solid tumors.

The inefficient tumor penetration of therapeutic antibodies has hampered their effective use in treating solid tumors. Here, we report the identification of a fully human single-domain antibody (UdAb), designated as n501, targeting the oncofetal antigen 5T4. The high-resolution crystal structure indicates that n501 adopts a compact structure very similar to that of camelid nanobodies, and binds tightly to all eight leucine-rich repeats of 5T4. Furthermore, the UdAb n501 exhibits exceptionally high stability, with no apparent activity changes over 4 weeks of storage at various temperatures. Importantly, the UdAb-based antibody-drug conjugate (n501-SN38) showed much deeper tumor penetration, significantly higher tumor uptake, and faster accumulation at tumor sites than conventional IgG1-based antibody-drug conjugate (m603-SN38), resulting in improved tumor inhibition. These results highlight the potential of UdAb-based antibody-drug conjugates as a potential class of antitumor therapeutics with characteristics of high stability and strong tumor penetration for the effective treatment of solid tumors.

Multi-Time Scale Trading Simulation of Source Grid Load Storage Based on Continuous Trading Mechanism for China.

The proportion of new energy in power systems is increasing yearly. How to deal with the adverse impact of new energy output uncertainty on its participation in trading from the mechanism level is an urgent problem in China that must be solved. A source grid load storage (SGLS) continuous trading mechanism and a multi-time scale trading simulation method are proposed which meet the needs of Chinese new energy consumption and satisfies the trading needs of Chinese power market players. Firstly, the connection mechanism of mid-long term, day-ahead, and intra-day SGLS interactive trading is established, and the meaning and ways of continuous development are defined. Secondly, the clearing model of SGLS trading based on the continuous trading mechanism is established to provide mathematical models and strategic methods for various resources to participate in SGLS trading. Then, the multi-time scale trading simulation of SGLS based on the continuous trading mechanism is carried out to obtain the trading strategies of different trading subjects. The example results show that compared with the trading mechanism based on deviation assessment, the one-day trading cost is reduced by 4.20% and the consumption rate of new energy is increased by 6.53%. It can be seen that the mid-long term-day-ahead-day SGLS interactive trading connection mechanism has advantages in reducing trading costs and improving the consumption rate of new energy. It can flexibly deal with the trading scenario of domestic new energy consumption and new energy reverse peak shaving, which has an effect on the adverse impact of trading and operation deviation caused by source load uncertainty on trading.

Metagenomic and metabolomic remodeling in nonagenarians and centenarians and its association with genetic and socioeconomic factors.

A better understanding of the biological and environmental variables that contribute to exceptional longevity has the potential to inform the treatment of geriatric diseases and help achieve healthy aging. Here, we compared the gut microbiome and blood metabolome of extremely long-lived individuals (94-105 years old) to that of their children (50-79 years old) in 116 Han Chinese families. We found extensive metagenomic and metabolomic remodeling in advanced age and observed a generational divergence in the correlations with socioeconomic factors. An analysis of quantitative trait loci revealed that genetic associations with metagenomic and metabolomic features were largely generation-specific, but we also found 131 plasma metabolic quantitative trait loci associations that were cross-generational with the genetic variants concentrated in six loci. These included associations between FADS1/2 and arachidonate, PTPA and succinylcarnitine and FLVCR1 and choline. Our characterization of the extensive metagenomic and metabolomic remodeling that occurs in people reaching extreme ages may offer new targets for aging-related interventions.

Transposon insertion mutation of Antarctic psychrotrophic fungus for red pigment production adaptive to normal temperature.

Polar regions are rich in microbial and product resources. Geomyces sp. WNF-15A is an Antarctic psy chrotrophic filamentous fungus producing high quality red pigment with potential for industrial use. However, efficient biosynthesis of red pigment can only realize at low temperature, which brings difficult control and high cost for the large-scale fermentation. This study aims to develop transposon insertion mutation method to improve cell growth and red pigment production adaptive to normal temperature. Genetic manipulation system of this fungus was firstly developed by antibiotic marker screening, protoplast preparation and transformation optimization, by which transformation efficiency of ∼50% was finally achieved. Then transposable insertion systems were established using Helitron, Fot1, and Impala transposons. The transposition efficiency reached 11.9%, 9.4%, and 4.6%, respectively. Mutant MP1 achieved the highest red pigment production (OD520 of 39) at 14°C, which was 40% higher than the wild-type strain. Mutant MP14 reached a maximum red pigment production (OD520 of 14.8) at 20°C, which was about twofold of the wild-type strain. Mutants MP2 and MP10 broke the repression mechanism of red pigment biosynthesis in the wild-type and allowed production at 25°C. For cell growth, eight mutants grew remarkably better (12%∼30% biomass higher) than the wild-type at 25°C. This study established an efficient genetic manipulation and transposon insertion mutation platform for polar filamentous fungus. It provides reference for genetic breeding of psychrotrophic fungi from polar and other regions.

Minos and Restless transposon insertion mutagenesis of psychrotrophic fungus for red pigment synthesis adaptive to normal temperature.

The polar psychrotrophic fungus Geomyces sp. WNF-15A can produce high-quality natural red pigment for the potential use as edible pigment. However, it shows low-temperature-dependent synthesis of red pigment, which limits its large-scale industrial applications due to the difficult and high-cost bioprocess control. This study aims to develop transposon-mediated mutagenesis methods to generate mutants that are able to synthesize red pigment at normal temperature. Four transposable systems, including single and dual transposable systems, were established in this fungus based on the Minos from Drosophila hydei and the Restless from Tolypocladium inflatum. A total of 23 production-dominant mutants and 12 growth-dominant mutants were thus obtained by constructed transposable systems. At 14 °C and 20 °C, the MPS1 mutant strain achieved the highest level of red pigment (OD520 of 43.3 and 29.7, respectively), which was increased by 78.4% and 128.7% compared to the wild-type, respectively. Of note, 4 mutants (MPS1, MPS3, MPS4 and MPD1) successfully synthesized red pigment (OD520 of 5.0, 5.3, 4.7 and 4.9, respectively) at 25 °C, which broke the limit of the wild-type production under normal temperature. Generally, the dual transposable systems of Minos and Restless were more efficient than their single transposable systems for mutagenesis in this fungus. However, the positive mutation ratios were similar between the dual and single transposable systems for either Minos or Restless. This study provides alternative tools for genetic mutagenesis breeding of fungi from extreme environments.