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.

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.

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.

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.

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.

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.

The effect of socioeconomic status on informal caregiving for parents among adult married females: evidence from China.

BACKGROUND: Married female caregivers face a higher risk of an informal care burden than other caregivers. No study has explored the effect of socioeconomic status (SES) on the intensity of informal care provided by married female caregivers in China. The purpose of this study is to empirically examine how the SES of married female caregivers affects the intensity of the informal care they provide for their parents/parents-in-law in China. METHODS: The data for this study were drawn from 8 waves of the China Health and Nutrition Survey (CHNS). The respondents were married women whose parents/parents-in-law needed care and lived in the same city as them. SES was defined based on four indicators: education, economic status, employment status, and hukou (China's household registration system). Informal caregivers were divided into three categories: non-caregivers (0 h/week), low-intensity caregivers (less than 10 h/week), and high-intensity caregivers (10 h/week and above). Multinomial logistic regression analysis was used to examine the relation between SES and the likelihood of a low- and high-intensity caregiving among married female caregivers, adjusting for age, family characteristics and survey wave. RESULTS: Of the 2661 respondents, high-intensity and low-intensity caregivers accounted for 16.35 and 21.27%, respectively. The multinomial logistic regression results showed that the likelihood of being a high-intensity caregiver versus (vs. a non-caregiver) increased as the caregiver's educational attainment increased (p < 0.05), and that high economic status was related to the likelihood of being a high-intensity caregiver, but this relationship was only significant at the 10% level. Urban females were 1.34 times more likely than their rural counterparts to provide low-intensity care vs. no care (p < 0.05) and were 1.33 times more likely to provide high-intensity care vs. no care (p < 0.05). Employed females were 1.25 times more likely than those unemployed females to provide low-intensity care vs. no care (p < 0.05). CONCLUSIONS: Differences in SES were found between high-intensity caregivers and low-intensity caregivers. Women with high educational attainment and urban hukou were more likely to provide high-intensity informal care, and women who were employed and had urban hukou were more likely to provide low-intensity care.

Socioeconomic inequity in inpatient service utilization based on need among internal migrants: evidence from 2014 national cross-sectional survey in China.

BACKGROUND: Providing equal treatment for those who have the same need for healthcare, regardless of their socioeconomic and cultural background, has become a shared goal among policymakers who strive to improve healthcare. This study aims to identify the socioeconomic status (SES) inequities in inpatient service utilization based on need among migrants by using a nationally representative study in China. METHODS: The data used in this study was derived from the 2014 National Internal Migrant Population Dynamic Monitoring Survey collected by the National Health Commission of China. The sampling frame for this study was taken using the stratified multistage random sampling method. All provincial urban belt and key cities were stratified, and 119 strata were finally determined. We used logistic regression method and Blinder-Oaxaca decomposition and calculated the concentration index to measure inequities of SES in inpatient service utilization based on need. Sample weights provided in the survey were applied in all the analysis and all standard errors in this study were clustered at the strata level. RESULTS: Of the total internal migrants, 18.75% unmet the inpatient service need. Results showed that inpatient service utilization concentrated among high-SES migrants (Concentration Index: 0.036, p < 0.001) and the decomposition results suggested that about 44.16% of the total SES gap in inpatient service utilization could be attributed to the gradient effect. After adjusting for other confounding variables, those had high school degree and university degree were more likely to meet the inpatient services need, and the OR values were 1.48 (95% CI 1.07, 2.03, p = 0.017) and 2.04 (95% CI 1.45, 2.88, p = 0.001), respectively. The OR values for Quartile 3 and Quartile 4 income groups was 1.28 (95% CI 1.01, 1.62, p = 0.044) and 1.37 (95% CI 1.02, 1.83, p = 0.035), respectively. CONCLUSION: This study observed an inequity in inpatient service utilization where the utilization concentrates among high SES migrants. It is important for policy makers to be aware of them and more intervention should be conducted.

Effect of social integration on childbirth return among internal migrant pregnant women: a nationally representative study in China.

BACKGROUND: Social integration has been demonstrated to be associated with the health care use among migrants, but few studies have focused on migrant pregnant women. This study aims to explore the association between social integration and childbirth at woman's hometown (childbirth return) of internal migrant pregnant women in China. METHOD: Using the data of "Monitoring Data of Chinese Migrants" in 2014, a total of 3412 internal migrant pregnant women were included in this study. Social integration was measured by economic integration, acculturation, and identification. The childbirth locations of internal migrant pregnant women were divided into current residency and the woman's hometown. Univariate logistic regression and two multivariable logistic regression models were employed to assess the association between social integration and childbirth return among internal migrant pregnant women. RESULT: Our study finds that 24.56% of migrant pregnant women choose to have a childbirth return. As for social integration, those who have their own house (OR = 0.351 95% CI 0.207-0.595) in current residence, who have been staying in current residence for at least 5 years (OR = 0.449; 95% CI 0.322-0.626), and who are willing to stay in the current residence for a long time (OR = 0.731; 95% CI 0.537-0.995) are less likely to have a childbirth return. Apart from social integration, our results also show that those migrant pregnant women who are older, who have higher education level, who have at least two family members in current residence, with a migration reason of work and business, who have established health record in the current residency, and who were not covered by medical insurances, are less likely to have a childbirth return. CONCLUSION: Social integration is negatively associated with childbirth return among internal migrant pregnant women in China. To improve the utilization of maternal care services for migrant pregnant women in current residence, targeted policies should be made to improve social integration status for migrant pregnant women.

LRScaf: improving draft genomes using long noisy reads.

BACKGROUND: The advent of third-generation sequencing (TGS) technologies opens the door to improve genome assembly. Long reads are promising for enhancing the quality of fragmented draft assemblies constructed from next-generation sequencing (NGS) technologies. To date, a few algorithms that are capable of improving draft assemblies have released. There are SSPACE-LongRead, OPERA-LG, SMIS, npScarf, DBG2OLC, Unicycler, and LINKS. Hybrid assembly on large genomes remains challenging, however. RESULTS: We develop a scalable and computationally efficient scaffolder, Long Reads Scaffolder (LRScaf, https://github.com/shingocat/lrscaf), that is capable of significantly boosting assembly contiguity using long reads. In this study, we summarise a comprehensive performance assessment for state-of-the-art scaffolders and LRScaf on seven organisms, i.e., E. coli, S. cerevisiae, A. thaliana, O. sativa, S. pennellii, Z. mays, and H. sapiens. LRScaf significantly improves the contiguity of draft assemblies, e.g., increasing the NGA50 value of CHM1 from 127.1 kbp to 9.4 Mbp using 20-fold coverage PacBio dataset and the NGA50 value of NA12878 from 115.3 kbp to 12.9 Mbp using 35-fold coverage Nanopore dataset. Besides, LRScaf generates the best contiguous NGA50 on A. thaliana, S. pennellii, Z. mays, and H. sapiens. Moreover, LRScaf has the shortest run time compared with other scaffolders, and the peak RAM of LRScaf remains practical for large genomes (e.g., 20.3 and 62.6 GB on CHM1 and NA12878, respectively). CONCLUSIONS: The new algorithm, LRScaf, yields the best or, at least, moderate scaffold contiguity and accuracy in the shortest run time compared with other scaffolding algorithms. Furthermore, LRScaf provides a cost-effective way to improve contiguity of draft assemblies on large genomes.

Antenatal care use and its determinants among migrant women during the first delivery: a nation-wide cross-sectional study in China.

BACKGROUND: Reasonable use of antenatal care (ANC) services by pregnant women played a crucial role in ensuring maternal and child safety and reducing the risk of complications, disability, and death in mothers and their infants. This study aimed to investigate the ANC use, and to explore the factors associated with ANC use among migrant women during the first delivery in China. METHODS: This study used the data of National Health and Family Planning Commission of People Republic of China in 2014. A total of 1505 migrant primiparous women were included in our current analysis. Frequencies and proportions were used to describe the data. Chi-square tests and multivariate binary logistic regression models were performed to explore the determinants that affect the number of times migrant women used ANC during their first delivery. RESULTS: Of the 1505 participants, 279 (18.54%) women received the ANC less than 5 times, and 1226 (81.46%) women used the ANC at least 5 times during the first delivery. The multivariate logistic regression model showed that migrant primiparous women with college and above education(P < 0.05;OR = 2.57;95%CI = 1.19-5.55), from the households with higher monthly income (P < 0.01;OR = 2.01;95%CI = 1.30-3.13), covered by maternity insurance(P < 0.01;OR = 2.01;95%CI = 1.28-3.18), with maternal health records (P < 0.001;OR = 2.44;95%CI = 1.61-3.69), migrating across county (P < 0.05;OR = 2.57;95%CI = 1.14-5.81), having migration experience before pregnancy(P < 0.05;OR = 1.37;95%CI = 1.03-1.81) were more likely to use ANC for at least five times. CONCLUSIONS: This study demonstrated that there were still some migrant maternal women (18.54%) who attended the ANC less than 5 times. Targeted policies should be developed to improve the utilization of ANC among migrant pregnant women.

Complex of EGCG with Cu(II) Suppresses Amyloid Aggregation and Cu(II)-Induced Cytotoxicity of α-Synuclein.

Accumulation of α-synuclein (α-Syn) is a remarkable pathology for Parkinson's disease (PD), therefore clearing it is possibly a promising strategy for treating PD. Aberrant copper (Cu(II)) homeostasis and oxidative stress play critical roles in the abnormal aggregation of α-Syn in the progress of PD. It is reported that the polyphenol (-)-epi-gallocatechin gallate (EGCG) can inhibit α-Syn fibrillation and aggregation, disaggregate α-Syn mature fibrils, as well as protect α-Syn overexpressed-PC12 cells against damage. Also, previous studies have reported that EGCG can chelate many divalent metal ions. What we investigate here is whether EGCG can interfere with the Cu(II) induced fibrillation of α-Syn and protect the cell viability. In this work, on a molecular and cellulaire basis, we demonstrated that EGCG can form a Cu(II)/EGCG complex, leading to the inhibition of Cu(II)-induced conformation transition of α-Syn from random coil to ß-sheet, which is a dominant structure in α-Syn fibrils and aggregates. Moreover, we found that the mixture of Cu(II) and EGCG in a molar ratio from 0.5 to 2 can efficiently inhibit this process. Furthermore, we demonstrated that in the α-Syn transduced-PC12 cells, EGCG can inhibit the overexpression and fibrillation of α-Syn in the cells, and reduce Cu(II)-induced reactive oxygen species (ROS), protecting the cells against Cu(II)-mediated toxicity.

Long-term survival trends of gastric cancer patients between 1972 and 2011 in Qidong.

BACKGROUND: There have been few reports on long-term survival of gastric cancer patients. This study analyzed the survival data of gastric cancer patients obtained from the population-based Qidong Cancer Registry between 1972 and 2011, providing a basis for evaluation of gastric cancer treatment and prognosis. METHODS: The cumulative observed survival rate and relative survival rate of gastric cancer patients were calculated using Hakulinen's method via the SURV3.01 software, which was developed by the Finnish Cancer Registry. The date of the last follow-up for the survival status of the 15,401 registered cases was April 30, 2012. RESULTS: The 1-, 5-, 10-, 20-, and 30-year observed survival rates were 33.82%, 14.18%, 10.35%, 6.63%, and 4.19%, respectively, and the 1-, 5-, 10-, 20-, and 30-year relative survival rates were 35.43%, 18.13%, 17.50%, 21.96%, and 32.84%, respectively. For males, the corresponding observed survival rates were 34.50%, 14.40%, 10.42%, 6.46%, and 4.05%, and the corresponding relative survival rates were 36.23%, 18.67%, 18.28%, 23.73%, and 38.61%. For females, the corresponding observed survival rates were 32.62%, 13.80%, 10.22%, 6.95%, and 4.46%, and the corresponding relative survival rates were 34.03%, 17.21%, 16.28%, 19.70%, and 26.78%. Significant differences in relative survival rates were observed between sexes (P = 0.003). For the 15-34, 35-44, 45-54, 55-64, 65-74, and 75+ age groups, the 5-year relative survival rates were 16.13%, 21.77%, 18.63%, 12.61%, 7.99%, and 2.94%, respectively, and the 10-year relative survival rates were 16.49%, 22.83%, 20.50%, 15.97%, 15.88%, and 15.73%, respectively. Remarkable improvement could be observed for the 5-, 10-, and 15-year relative survival rates in Qidong beginning in the 1980s. CONCLUSION: The survival outcome of registered gastric cancer cases in Qidong showed gradual progress over the past two decades.

Female breast cancer survival in Qidong, China, 1972-2011: a population-based study.

BACKGROUND: Based on data from the population-based Qidong Cancer Registry, we report a survival analysis for female breast cancer patients diagnosed during 1972-2011 in order to assess the long-term trends for the prognosis of this cancer. METHODS: The last follow-up for survival status of the 3,398 registered female breast cancer cases was April, 2012. Cumulative observed survival (OS) and relative survival (RS) rates were calculated using Hakulinen's method performed by the SURV3.01 Software developed at the Finnish Cancer Registry. RESULTS: The one-, three-, five-, ten-, fifteen-, twenty-, thirty-, and forty- year OS rates were 83.61%, 67.53%, 58.75%, 48.56%, 42.57%, 38.30%, 29.19%, 19.35%; and the RS rates were 84.76%, 70.45%, 63.12%, 56.81%, 55.26%, 56.36%, 62.59%, 84.00%, respectively. Five-year RS rates of age groups 15-34, 35-44, 45-54, 55-64, 65-74, and 75+ were 60.17%, 68.27%, 67.79%, 56.03%, 55.50%, and 57.28%; 10-year RS rates were 54.16%, 59.59%, 61.34%, 47.78%, 51.30%, and 59.28%, respectively. There were statistical differences among the age groups (RS: χ2 = 152.15, P = 0.000). Remarkable improvement could be seen for the 5-year RS rates from 52.08% in 1972 to 69.26% in 2003-2007, and the 10-year RS rates from 43.16% in 1972 to 60.85% in 1998-2002, respectively. CONCLUSIONS: Survival outcomes from Qidong registered cases with breast cancer have shown gradual progress during the past 40 years. The disparities between survival rates of this area and developed countries are getting narrower, but there is still great need for improving survival in Qidong.

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.

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.

Comparative plastome analyses and evolutionary relationships of 25 East Asian species within the medicinal plant genus Scrophularia (Scrophulariaceae).

Backgroud: Scrophularia L., a genus of the Scrophulariaceae, is a group of important medicinal plants used for eliminating heat and detoxifying. East Asia has an abundance of potentially medicinal Scrophularia species, and it serves as a secondary diversity center of the genus. However, the genomic resources available for germplasm identification and pharmaceutical exploration of East Asian Scrophularia are insufficient, hindering its commercial and industrial development. Additionally, the interspecific relationships of most East Asian Scrophularia species remain unclear. Methods: In this study, we sequenced the leaves of 25 East Asian species of the genus Scrophularia, assembled and annotated the complete chloroplast genomes, and subsequently performed comparative and phylogenetic analyses on these genomes. Results and discussion: The conserved plastome length of these 25 species ranged from 151,582 bp to 153,239 bp, containing a total of 132 coding genes, including 18 duplicated genes and 114 unique genes. Through genome alignment of these 25 species, 38-53 repeated sequences and 7 shared SSRs were identified, along with regions with high nucleotide polymorphism (Pi), which could potentially serve as molecular markers for species identification. The genome structure, gene content, and arrangement showed conservation, while variations were observed in the IR boundary regions and IGS. Phylogenetic inferences based on whole plastomes or on coding sequences (CDS) only yielded congruent results. We categorized the 25 East Asian Scrophularia species into six distinct clades and further explored their interspecies relationships using morphological characteristics, such as flower color, the relative position of stamens and corolla, and plant height. This could lay a genetic basis for future resource development of Scrophularia in East Asia.

Single-cell RNA sequencing reveals dynamics of gene expression for 2D elongation and 3D growth in Physcomitrium patens.

The transition from two-dimensional (2D) to 3D growth likely facilitated plants to colonize land, but its heterogeneity is not well understood. In this study, we utilized single-cell RNA sequencing to analyze the moss Physcomitrium patens, whose morphogenesis involves a transition from 2D to 3D growth. We profiled over 17,000 single cells covering all major vegetative tissues, including 2D filaments (chloronema and caulonema) and 3D structures (bud and gametophore). Pseudotime analyses revealed larger numbers of candidate genes that determine cell fates for 2D tip elongation or 3D bud differentiation. Using weighted gene co-expression network analysis, we identified a module that connects ß-type carbonic anhydrases (ßCAs) with auxin. We further validated the cellular expression patterns of ßCAs and demonstrated their roles in 3D gametophore development. Overall, our study provides insights into cellular heterogeneity in a moss and identifies molecular signatures that underpin the 2D-to-3D growth transition at single-cell resolution.

Ethical concerns in aging research: perspectives of global frontline researchers.

This study investigated the ethical landscape of aging research amid the increasing global focus on extending the human lifespan and health span. Our global survey of 180 researchers across 38 jurisdictions revealed divergent perceptions of aging, a consensus regarding the feasibility of delaying aging, and multiple perspectives regarding lifespan extension. The present findings underscore a paradigm shift toward inclusive and ethically sound research, emphasizing the need for an approach that strikes a balance between basic and clinical research. In addition, this study highlighted key ethical concerns in aging research, including the effects of misleading advertising, potential inequality in access to aging interventions, and risks pertaining to the extrapolation of research findings from lower-model organisms to humans. The insights presented in this paper call for an integrated approach for overcoming the complex ethical and societal challenges in aging research to ensure responsible and equitable advancements in this burgeoning field.

GSC: efficient lossless compression of VCF files with fast query.

BACKGROUND: With the rise of large-scale genome sequencing projects, genotyping of thousands of samples has produced immense variant call format (VCF) files. It is becoming increasingly challenging to store, transfer, and analyze these voluminous files. Compression methods have been used to tackle these issues, aiming for both high compression ratio and fast random access. However, existing methods have not yet achieved a satisfactory compromise between these 2 objectives. FINDINGS: To address the aforementioned issue, we introduce GSC (Genotype Sparse Compression), a specialized and refined lossless compression tool for VCF files. In benchmark tests conducted across various open-source datasets, GSC showcased exceptional performance in genotype data compression. Compared with the industry's most advanced tools (namely, GBC and GTC), GSC achieved compression ratios that were higher by 26.9% to 82.4% over GBC and GTC on the datasets, respectively. In lossless compression scenarios, GSC also demonstrated robust performance, with compression ratios 1.5× to 6.5× greater than general-purpose tools like gzip, zstd, and BCFtools-a mode not supported by either GBC or GTC. Achieving such high compression ratios did require some reasonable trade-offs, including longer decompression times, with GSC being 1.2× to 2× slower than GBC, yet 1.1× to 1.4× faster than GTC. Moreover, GSC maintained decompression query speeds that were equivalent to its competitors. In terms of RAM usage, GSC outperformed both counterparts. Overall, GSC's comprehensive performance surpasses that of the most advanced technologies. CONCLUSION: GSC balances high compression ratios with rapid data access, enhancing genomic data management. It supports seamless PLINK binary format conversion, simplifying downstream analysis.