Constructing Stiffness Tunable DNA Hydrogels Based on DNA Modules with Adjustable Rigidity.

DNA hydrogel represents a potent material for crafting biological scaffolds, but the toolbox to systematically regulate the mechanical property is still limited. Herein, we have provided a strategy to tune the stiffness of DNA hydrogel through manipulating the rigidity of DNA modules. By introducing building blocks with higher molecular rigidity and proper connecting fashion, DNA hydrogel stiffness could be systematically elevated. These hydrogels showed excellent dynamic properties and biocompatibility, thus exhibiting great potential in three-dimensional (3D) cell culture. This study has offered a systematic method to explore the structure-property relationship, which may contribute to the development of more intelligent and personalized biomedical platforms.

Genome-wide detection of selection signatures in Jianli pigs reveals novel cis-regulatory haplotype in EDNRB associated with two-end black coat color.

BACKGROUND: Jianli pig, a renowned indigenous breed in China, has the characteristics of a two-end black (TEB) coat color, excellent meat quality, strong adaptability and increased prolificacy. However, there is limited information available regarding the genetic diversity, population structure and genomic regions under selection of Jianli pig. On the other hand, the genetic mechanism of TEB coat color has remained largely unknown. RESULTS: In this study, the whole genome resequencing of 30 Jianli pigs within a context of 153 individuals representing 13 diverse breeds was performed. The population structure analysis revealed that Jianli pigs have close genetic relationships with the Tongcheng pig breed, their geographical neighbors. Three methods (observed heterozygosity, expected heterozygosity, and runs of homozygosity) implied a relatively high level of genetic diversity and, a low inbreeding coefficient in Jianli compared with other pigs. We used Fst and XP-EHH to detect the selection signatures in Jianli pigs compared with Asian wild boar. A total of 451 candidate genes influencing meat quality (CREBBP, ADCY9, EEPD1 and HDAC9), reproduction (ESR1 and FANCA), and coat color (EDNRB, MITF and MC1R), were detected by gene annotation analysis. Finally, to fine-map the genomic region for the two-end black (TEB) coat color phenotype in Jianli pigs, we performed three signature selection methods between the TEB coat color and no-TEB coat color pig breeds. The current study, further confirmed that the EDNRB gene is a candidate gene for TEB color phenotype found in Chinese pigs, including Jinhua pigs, and the haplotype harboring 25 SNPs in the EDNRB gene may promote the formation of TEB coat color. Further ATAC-seq and luciferase reporter assays of these regions suggest that the 25-SNPs region was a strong candidate causative mutation that regulates the TEB coat color phenotype by altering enhancer function. CONCLUSION: Our results advanced the understanding of the genetic mechanism behind artificial selection, and provided further resources for the protection and breeding improvement of Jianli pigs.

Transposition mechanism of ISApl1-the determinant of colistin resistance dissemination.

Multidrug-resistant Enterobacteriaceae, a prominent family of gram-negative pathogenic bacteria, causes a wide range of severe diseases. Strains carrying the mobile colistin resistance (mcr-1) gene show resistance to polymyxin, the last line of defense against multidrug-resistant gram-negative bacteria. However, the transmission of mcr-1 is not well understood. In this study, genomes of mcr-1-positive strains were obtained from the NCBI database, revealing their widespread distribution in China. We also showed that ISApl1, a crucial factor in mcr-1 transmission, is capable of self-transposition. Moreover, the self-cyclization of ISApl1 is mediated by its own encoded transposase. The electrophoretic mobility shift assay experiment validated that the transposase can bind to the inverted repeats (IRs) on both ends, facilitating the cyclization of ISApl1. Through knockout or shortening of IRs at both ends of ISApl1, we demonstrated that the cyclization of ISApl1 is dependent on the sequences of the IRs at both ends. Simultaneously, altering the ATCG content of the bases at both ends of ISApl1 can impact the excision rate by modifying the binding ability between IRs and ISAPL1. Finally, we showed that heat-unstable nucleoid protein (HU) can inhibit ISApl1 transposition by binding to the IRs and preventing ISAPL1 binding and expression. In conclusion, the regulation of ISApl1-self-circling is predominantly controlled by the inverted repeat (IR) sequence and the HU protein. This molecular mechanism deepens our comprehension of mcr-1 dissemination.

Heterologous overexpression of heat shock protein 20 genes of different species of yellow Camellia in Arabidopsis thaliana reveals their roles in high calcium resistance.

Yellow Camellia (Camellia sect. chrysantha) is a rare ornamental plant and an important germplasm resource globally. Camellia nitidissima thrives in normal acidic soils, while Camellia limonia can adapt to the calcareous soils found in karst areas. Our previous study on the karst adaptation of yellow camellias revealed that the expression levels of heat shock protein 20(HSP20) were higher in Camellia limonia than in Camellia nitidissima. However, the functions of the HSP20 gene of Camellia limonia remain unclear to data. In this study, the HSP20 genes of Camellia limonia (ClHSP20-OE lines) and Camellia. nitidissima (CnHSP20-OE lines) were cloned and overexpressed heterologously in Arabidopsis thaliana. Additionally, we overexpressed the HSP20 gene of Arabidopsis (AtHSP20-OE lines) was also overexpressed, and the T-DNA inserted mutants (athspmutant lines) were also used to determine the functions of HSP20 genes. Under high calcium stress, the chlorophyll, nitrogen, water content and humidity of leaves were increased in ClHSP20-OE lines, while those of other lines were declined. The size of the stomatal apertures, stomatal conductance, and the photosynthetic efficiency of ClHSP20-OE lines were higher than those of the other lines. However, the accumulation of H2O2 and O2- in the leaves of ClHSP20-OE lines was the lowest among all the lines. Energy spectrum scanning revealed that the percentage of calcium on the surfaces of the leaves of ClHSP20-OE lines was relatively low, while that of athspmutant lines was the highest. The ClHSP20 gene can also affected soil humidity and the contents of soil nitrogen, phosphorus, and potassium. Transcriptome analysis revealed that the expressions of FBA5 and AT5G10770 in ClHSP20-OE lines was significantly up-regulated compared to that of CnHSP20-OE lines. Compared to that of athspmutant lines, the expressions of DREB1A and AT3G30460 was significantly upregulated in AtHSP20-OE lines, and the expression of POL was down-regulated. Our findings suggest that the HSP20 gene plays a crucial role in maintained photosynthetic rate and normal metabolism by regulating the expression of key genes under high-calcium stress. This study elucidates the mechanisms underlying the karst adaptation in Camellia. limonia and provides novel insights for future research on karst plants.

Strong Yet Tough Transparent Paper with Superb Foldability.

Transparent paper manufactured from wood fibers is emerging as a promising, cost-effective, and carbon-neutral alternatives to plastics. However, fully exploring their mechanical properties is one of the most pressing challenges. In this work, a strong yet tough transparent paper with superior folding endurance is prepared by rationally altering the native fiber structure. Microwave-assisted choline chloride/lactic acid deep eutectic solvent (DES) pulping is first utilized to isolate wood fibers from spruce wood. During this process, the S1 layer within the fibers is partially disrupted, forming protruding microfibrils that play a crucial role in enhancing cellulose accessibility. Subsequently, carboxymethylation treatment is applied to yield uniformly swollen carboxymethylated wood fibers (CM fibers), which improves the interaction between CM fibers during papermaking. The as-prepared transparent paper not only shows a 90% light transmittance (550 nm) but also exhibits impressive mechanical properties, including a folding endurance of over 26 000, a tensile strength of 248.4 MPa, and a toughness of 15.6 MJ m-3. This work provides a promising route for manufacturing transparent paper with superior mechanical properties from wood fibers and can extend their use in areas normally dominated by high-performance nonrenewable plastics.

Enhancing Orbital Interaction in Spinel LiNi0.5Mn1.5O4 Cathode for High-Voltage and High-Rate Li-Ion Batteries.

High voltage cobalt-free spinel LiNi0.5Mn1.5O4 (LNMO) is well organized as a high-power cathode material for lithium (Li)-ion batteries, however, the weak interaction between the 3d orbital of the transition metal (TM) ions and the 2p orbital of oxygen (O) leads to the instability of crystal structural, hindering the long-term stable cycling of LNMO cathode especially at high temperatures. Here, a design strategy of orbital interaction is initiated to strengthen TM 3d-O 2p framework in P-doped LNMO (P-LNMO) by choosing phytic acid as P dopant, which can realize more uniform doping compared to regular phosphate. The results show that the enhancement of TM 3d-O 2p orbital interaction in P-LNMO can suppress the Jahn-Teller effect and subsequent dissolution of Mn, as well as lowers the energy barrier for Li ion insertion/extraction kinetics. As a result, superior electrochemical performances including high discharge capacity, stable cycling behavior and enhanced rate capability of P-LNMO are obtained. Significantly, the P-LNMO pouch cell shows great cycling stability with 97.4% capacity retention after 100 cycles.

An induced mutation of ABC-transporter component VraF(K84E) contributes to vancomycin resistance and virulence in Staphylococcus aureus strain MW2.

Staphylococcus aureus is a notorious pathogen responsible for various severe diseases. Due to the emergence of drug-resistant strains, the prevention and treatment of S. aureus infections have become increasingly challenging. Vancomycin is considered to be one of the last-resort drugs for treating most methicillin-resistant S. aureus (MRSA), so it is of great significance to further reveal the mechanism of vancomycin resistance. VraFG is one of the few important ABC (ATP-binding cassette) transporters in S. aureus that can form TCS (two-component systems)/ABC transporter modules. ABC transporters can couple the energy released from ATP hydrolysis to translocate solutes across the cell membrane. In this study, we obtained a strain with decreased vancomycin susceptibility after serial passaging and selection. Subsequently, whole-genome sequencing was performed on this laboratory-derived strain MWA2 and a novel single point mutation was discovered in vraF gene, leading to decreased sensitivity to vancomycin and daptomycin. Furthermore, the mutation reduces autolysis of S. aureus and downregulates the expression of lytM, isaA, and atlA. Additionally, we observed that the mutant has a less net negative surface charge than wild-type strain. We also noted an increase in the expression of the dlt operon and mprF gene, which are associated with cell surface charge and serve to hinder the binding of cationic peptides by promoting electrostatic repulsion. Moreover, this mutation has been shown to enhance hemolytic activity, expand subcutaneous abscesses, reflecting an increased virulence. This study confirms the impact of a point mutation of VraF on S. aureus antibiotic resistance and virulence, contributing to a broader understanding of ABC transporter function and providing new targets for treating S. aureus infections.

Elevated circulating BMP9 aggravates pulmonary angiogenesis in hepatopulmonary syndrome rats through ALK1-Endoglin-Smad1/5/9 signalling.

BACKGROUND: Bone morphogenetic protein 9 (BMP9) is a hepatokine that plays a pivotal role in the progression of liver diseases. Moreover, an increasing number of studies have shown that BMP9 is associated with hepatopulmonary syndrome (HPS), but its role in HPS is unclear. Here, we evaluated the influence of CBDL on BMP9 expression and investigated potential mechanisms of BMP9 signalling in HPS. METHODS: We profiled the circulating BMP9 levels in common bile duct ligation-induced HPS rat model, and then investigated the effects and mechanisms of HPS rat serum on pulmonary vascular endothelial dysfunction in rat model, as well as in primarily cultured rat pulmonary microvascular endothelial cells. RESULTS: Our data revealed that circulating BMP9 levels were significantly increased in the HPS rats compared to control group. Besides, the elevated BMP9 in HPS rat serum was not only crucial for promoting endothelial cell proliferation and tube formation through the activin receptor-like kinase1 (ALK1)-Endoglin-Smad1/5/9 pathway, but also important for accumulation of monocytes. Treatments with ALK1-Fc or silencing ALK1 expression to inhibit the BMP9 signalling pathway effectively eliminated these effects. In agreement with these observations, increased circulating BMP9 was associated with an increase in lung vessel density and accumulation of pro-angiogenic monocytes in the microvasculature in HPS rats. CONCLUSIONS: This study provided evidence that elevated circulating BMP9, secreted from the liver, promote pulmonary angiogenesis in HPS rats via ALK1-Endoglin-Smad1/5/9 pathway. In addition, BMP9-regulated pathways are also involved in accumulation of pro-angiogenic monocytes in the pulmonary microvasculature in HPS rats.

The role of regulatory T cells in vitiligo and therapeutic advances: a mini-review.

BACKGROUND: Regulatory T cells (Tregs) play vital roles in controlling immune reactions and maintaining immune tolerance in the body. The targeted destruction of epidermal melanocytes by activated CD8+T cells is a key event in the development of vitiligo. However, Tregs may exert immunosuppressive effects on CD8+T cells, which could be beneficial in treating vitiligo. METHODS: A comprehensive search of PubMed and Web of Science was conducted to gather information on Tregs and vitiligo. RESULTS: In vitiligo, there is a decrease in Treg numbers and impaired Treg functions, along with potential damage to Treg-related signaling pathways. Increasing Treg numbers and enhancing Treg function could lead to immunosuppressive effects on CD8+T cells. Recent research progress on Tregs in vitiligo has been summarized, highlighting various Treg-related therapies being investigated for clinical use. The current status of Treg-related therapeutic strategies and potential future directions for vitiligo treatment are also discussed. CONCLUSIONS: A deeper understanding of Tregs will be crucial for advancing Treg-related drug discovery and treatment development in vitiligo.

The complete genome sequence of a putative novel cytorhabdovirus identified in Chelidonium majus in China.

A new cytorhabdovirus, tentatively named "chelidonium yellow mottle associated virus" (CheYMaV), was identified in Chelidonium majus with yellow mottle symptoms by high-throughput sequencing and RT-PCR. Its genome is 12,121 nucleotides in length and contains eight open reading frames (ORFs) in the order 3'-N-P'-P-P3-M-G-P6-L-5'. Amino acid sequence comparisons between the putative proteins of CheYMaV and the corresponding proteins of other cytorhabdoviruses showed that it shares the highest sequence similarity with Trifolium pratense virus A (TpVA, MH982250) and Glehnia littoralis virus 1 (GllV1, BK014304), but with sequence identity values below the species demarcation threshold for cytorhabdoviruses (< 80%). Phylogenetic analysis showed that CheYMaV is most closely related to TpVA and GllV1. CheYMaV should therefore be considered a new member of the genus Cytorhabdovirus. This is the first report of a cytorhabdovirus identified in Chelidonium majus.

Gradually Self-Strengthen DNA Supramolecular Hydrogels.

The dynamic mechanical strength of the extracellular matrix (ECM) has been demonstrated to play important role in determining the cell behavior. Growing evidences suggest that the gradual stiffening process of the matrix is particularly decisive during tissue development and wound healing. Herein, a novel strategy to prepare hydrogels with gradually enhanced mechanical strength is provided. Such hydrogels could maintain the dynamic properties at their initial states, such as self-healing and shear-thinning properties. With subsequent slow covalent crosslinking, the stability and mechanical properties would be gradually improved. This method is useful for sequence programmability and oxidation strategies, which has provided an alternated tool to study cell behavior during dynamic increase in mechanical strength of ECM.

A novel prognostic index for extranodal natural killer/T-cell lymphoma in the era of pegaspargase/L-asparaginase.

Aim: This multicenter retrospective study aimed to develop a novel prognostic system for extranodal natural killer/T-cell lymphoma (ENKTL) patients in the era of pegaspargase/L-asparaginase. Materials & methods: A total of 844 newly diagnosed ENKTL patients were included. Results: Multivariable analysis confirmed that Eastern Cooperative Oncology Group performance status, lactate dehydrogenase, Chinese Southwest Oncology Group and Asia Lymphoma Study Group ENKTL (CA) system, and albumin were independent prognostic factors. By rounding up the hazard ratios from four significant variables, a maximum of 7 points were assigned. The model of Huaihai Lymphoma Working Group-Natural killer/T-cell Lymphoma prognostic index (NPI) was identified with four risk groups and the 5-year overall survival was 88.2, 66.7, 54.3 and 30.5%, respectively. Conclusion: Huaihai Lymphoma Working Group-NPI provides a feasible stratification system for patients with ENKTL in the era of pegaspargase/L-asparaginase.

[Box: see text].

Overexpression of MPV17/PMP22-like protein 2 gene decreases production of radical oxygen species in Pyropia yezoensis (Bangiales, Rhodophyta).

The northward shift of Pyropia yezoensis aquaculture required the breeding of germplasms with tolerance to the oxidative stress due to the high light conditions of the North Yellow Sea area. The MPV17/PMP22 family proteins were identified as a molecule related to reactive oxygen species (ROS) metabolism. Here, one of the MPV17 homolog genes designated as PyM-LP2 was selected for functional identification by introducing the encoding sequence region/reverse complementary fragment into the Py. yezoensis genome. Although the photosynthetic activity, the respiratory rate, and the ROS level in wild type (WT) and different gene-transformed algal strains showed similar levels under normal conditions, the overexpression (OE) strain exhibited higher values of photosynthesis, respiration, and reducing equivalents pool size but lower intracellular ROS production under stress conditions compared with the WT. Conversely, all the above parameters showed opposite variation trends in RNAi strain as those in the OE strain. This implied that the PyM-LP2 protein was involved in the mitigation of the oxidative stress. Sequence analysis revealed that this PyM-LP2 protein was assorted to peroxisomes and might serve as a poring channel for transferring malate (Mal) to peroxisomes. By overexpressing PyM-LP2, the transfer of Mal from chloroplasts to peroxisomes was enhanced under stress conditions, which promoted photorespiration and ultimately alleviated excessive reduction of the photosynthetic electron chain. This research lays the groundwork for the breeding of algae with enhanced resistance to oxidative stresses.

Remediation of arsenic-contaminated soil using nanoscale schwertmannite synthesized by persulfate oxidation with carboxymethyl cellulose stabilization.

Schwertmannite (SCH) is a promising material for adsorbing inorganic arsenic (As). We synthesized SCH nanoparticles (nano-SCH) via a modified chemical oxidation method and investigated the application of nano-SCH for the remediation of As-contaminated soils. The production of nano-SCH was successfully prepared using the persulfate oxidation method with carboxymethyl cellulose stabilization. The spherical structure of the nano-SCH particles had an average hydrodynamic diameter of 296 nm with high specific surface areas (108.9 m2/g). Compared with SCH synthesized via the H2O2 oxidation method, the percentage of Fe3+ precipitation in nano-SCH synthesis increased from 63.2% to 84.1%. The inorganic As adsorption capacity of nano-SCH improved by 2.27 times at solution pH = 6. After remediation of heavily As-contaminated soils by using 5% nano-SCH, the leachability of inorganic As rapidly decreased to 0.01% in 30 d. Correspondingly, the immobilization efficiencies of inorganic As in soil reached >99.9%. The inorganic As fractions in treated soil shifted from specifically and nonspecifically bound forms to amorphous and crystalline hydrous oxide-bound fractions. After treatment with 5% nano-SCH for 60 d, soil pH slightly decreased from 5.47 to 4.94; by contrast, soil organic matter content increased by 20.9%. Simultaneously, dehydrogenase concentration in soil decreased by 22.4%-34.7% during the remediation process. These changes in soil properties and As immobilization jointly decreased microbial activity and initiated the re-establishment of bacterial communities in the soil. In summary, this study presents a novel and high-productivity technology for nano-SCH synthesis and confirms the high As immobilization effectiveness of nano-SCH in the remediation of As-contaminated soils.

Tumor-specific enhanced NIR-II photoacoustic imaging via photothermal and low-pH coactivated AuNR@PNIPAM-VAA nanogel.

BACKGROUND: Properly designed second near-infrared (NIR-II) nanoplatform that is responsive tumor microenvironment can intelligently distinguish between normal and cancerous tissues to achieve better targeting efficiency. Conventional photoacoustic nanoprobes are always "on", and tumor microenvironment-responsive nanoprobe can minimize the influence of endogenous chromophore background signals. Therefore, the development of nanoprobe that can respond to internal tumor microenvironment and external stimulus shows great application potential for the photoacoustic diagnosis of tumor. RESULTS: In this work, a low-pH-triggered thermal-responsive volume phase transition nanogel gold nanorod@poly(n-isopropylacrylamide)-vinyl acetic acid (AuNR@PNIPAM-VAA) was constructed for photoacoustic detection of tumor. Via an external near-infrared photothermal switch, the absorption of AuNR@PNIPAM-VAA nanogel in the tumor microenvironment can be dynamically regulated, so that AuNR@PNIPAM-VAA nanogel produces switchable photoacoustic signals in the NIR-II window for tumor-specific enhanced photoacoustic imaging. In vitro results show that at pH 5.8, the absorption and photoacoustic signal amplitude of AuNR@PNIPAM-VAA nanogel in NIR-II increases up obviously after photothermal modulating, while they remain slightly change at pH 7.4. Quantitative calculation presents that photoacoustic signal amplitude of AuNR@PNIPAM-VAA nanogel at 1064 nm has ~ 1.6 folds enhancement as temperature increases from 37.5 °C to 45 °C in simulative tumor microenvironment. In vivo results show that the prepared AuNR@PNIPAM-VAA nanogel can achieve enhanced NIR-II photoacoustic imaging for selective tumor detection through dynamically responding to thermal field, which can be precisely controlled by external light. CONCLUSIONS: This work will offer a viable strategy for the tumor-specific photoacoustic imaging using NIR light to regulate the thermal field and target the low pH tumor microenvironment, which is expected to realize accurate and dynamic monitoring of tumor diagnosis and treatment.

Effect of ropivacaine, mepivacaine or the combination of ropivacaine and mepivacaine for epidural anaesthesia on the postoperative recovery in patients undergoing caesarean section: a randomized, prospective, double-blind study.

BACKGROUND: Anaesthetic methods and drugs with rapid onset, rapid recovery and better postoperative analgesia are more suitable for rapid recovery in obstetric anaesthesia. We formulated the following hypothesis: a combination of mepivacaine and ropivacaine could provide a longer analgesic effect and have more advantages in terms of rapid-recovery indicators. METHODS: A total of 180 pregnant women scheduled to undergo elective caesarean sections were randomly assigned to three surgical groups, which received 2% mepivacaine (Group M), 2% mepivacaine + 0.75% ropivacaine (Group MR) (Volume 1:1) or 0.75% ropivacaine (Group R) through an epidural catheter. The situation of postoperative analgesia and other indicators of rapid recovery were recorded. RESULTS: One hundred and fifty patients were included in the final analysis. Their demographic data were similar. The visual analogue scale (VAS) scores of Group MR and Group R were lower than Group M at 1 and 2 h after surgery both at rest and with movement (P < 0.05), and the time to first ambulation in Group MR (17.38 ± 2.06 h) and Group M (17.20 ± 2.09 h) was shorter than that in Group R (22.18 ± 1.74 h) (P < 0.05). CONCLUSION: Application of 2% mepivacaine combined with 0.75% ropivacaine for epidural anaesthesia can provide longer postoperative analgesia and earlier ambulation, these effect may be more suitable than that of 2% mepivacaine or 0.75% ropivacaine alone for caesarean section. TRIAL REGISTRATION: This study was registered at Chinese Clinical Trial Registry (Registration number: ChiCTR 2300078288; date of registration: 04/12/2023).

Carfilzomib activates ER stress and JNK/p38 MAPK signaling to promote apoptosis in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly cancers in the world, which is frequently diagnosed at a late stage. HCC patients have a poor prognosis due to the lack of an efficacious therapeutic strategy. Approved drug repurposing is a way for accelerating drug discovery and can significantly reduce the cost of drug development. Carfilzomib (CFZ) is a second-generation proteasome inhibitor, which is highly efficacious against multiple myeloma and has been reported to possess potential antitumor activities against multiple cancers. However, the underlying mechanism of CFZ on HCC is still unclear. Here, we show that CFZ inhibits the proliferation of HCC cells through cell cycle arrest at the G2/M phase and suppresses the migration and invasion of HCC cells by inhibiting epithelial-mesenchymal transition. We also find that CFZ promotes reactive oxygen species production to induce endoplasmic reticulum (ER) stress and activate JNK/p38 MAPK signaling in HCC cells, thus inducing cell death in HCC cells. Moreover, CFZ significantly inhibits HCC cell growth in a xenograft mouse model. Collectively, our study elucidates that CFZ impairs mitochondrial function and activates ER stress and JNK/p38 MAPK signaling, thus inhibiting HCC cell and tumor growth. This indicates that CFZ has the potential as a therapeutic drug for HCC.

Genetic Variability of CYP4F2, CYP2D6, CYP2E1, and ACE in the Chinese Yi Population.

Genetic polymorphisms of very important pharmacogenes (VIP) are a significant factor contributing to inter-individual variability in drug therapy. The purpose of this study was to identify significantly different loci in the Yi population and to enrich their pharmacogenomic information. 54 VIP variants were selected from the Pharmacogenomics Knowledge Base (PharmGKB) and genotyped in 200 Yi individuals. Then, we compared their genotype distribution between the Yi population and the other 26 populations using the χ2 test. Compared with the other 26 populations, the genotype frequencies of 4 single nucleotide polymorphisms (SNPs), rs2108622 (CYP4F2), rs1065852 (CYP2D6), rs2070676 (CYP2E1), and rs4291 (ACE), had significant differences in the Yi population. For example, the TT genotype frequency of rs2108622 (8.1%) was higher than that of African populations, and the AA genotype frequency of rs1065852 (27.3%) was higher than that of other populations except East Asians. We also found that the Yi populations differed the least from East Asians and the most from Africans. Furthermore, the differences in these variants might be related to the effectiveness and toxicity risk of using warfarin, iloperidone, cisplatin cyclophosphamide, and other drugs in the Yi population. Our data complement the pharmacogenomic information of the Yi population and provide theoretical guidance for their personalized treatment.

T-2 toxin-induced testicular impairment by triggering oxidative stress and ferroptosis.

T-2 toxin is a trichothecene mycotoxin of significant danger to humans and animals. Its impact on reproductive toxicity is attributed to oxidative stress, which ultimately leads to cell death. Ferroptosis is a programmed cell death that characterized by lipid peroxidation. This study aimed to investigate the toxic effects of T-2 toxin on mouse testis and the potential mechanism of T-2 toxin-induced ferroptosis. T-2 toxin significantly altered the morphology of the testis and decreased testosterone level, sperm concentration, and increased sperm malformation rate, as well as induced oxidative damage with reactive oxygen species and malondialdehyde accumulated, and activity of superoxide dismutase, glutathione peroxidase decreased. Additionally, T-2 toxin induced ferroptosis by accumulating iron ions, increasing prostaglandin endoperoxide synthase 2, downregulating glutathione peroxidase 4 and ferritin heavy chain 1, as well as manifesting ferroptotic morphological alterations, ultimately leading to testicular impairment. Administration of ferroptosis inhibitor liproxstatin-1 or antioxidant resveratrol effectively mitigated the T-2 toxin-induced ferroptosis and testicular injury. These findings provided novel insights into the fundamental mechanism of T-2 toxin-induced cell death and furnished further proof of the potential therapeutic effect in addressing T-2 toxin-induced testicular impairment.

First report of cucumber green mottle mosaic virus infecting Cynanchum rostellatum in China.

Cucumber green mottle mosaic virus (CGMMV) was first discovered on cucumber in the United Kingdom in 1935 (Ainsworth, 1935), and has spread worldwide except to Antarctica (Jones, 2021). Given its extensive damage, it is considered an important pathogen on global cucurbit plants and fruit crops. In China, CGMMV was first reported on pumpkin in Guangxi Province in 2003 (Qin et al., 2005), and occurred on 34 plants species across 23 provinces (Liu et al., 2016). Cynanchum rostellatum is a member of the family Apocynaceae. In July 2021, leaves of C. rostellatum exhibiting virus-like symptoms (yellowing, severe crinkling, deformation) were observed and collected in Liaoning Province, China. Aphids were also observed on the leaves and stems (Fig. S1) of the plants and were collected. Total RNA was extracted from diseased leaves following the CTAB method, followed by the depletion of ribosomal RNAs (rRNA) with TIANSeq rRNA Depletion Kit (Tiangen, China). The RNAs were, then processed into a DNBSEQ LncRNA-Seq library, and sequenced on the MGISEQ-2000 platform at BGI Genomics (Wuhan, China). A total of 106.98 M clean reads were obtained after data filtering using SOAPnuke software (BGI, China). The clean reads were assembled into contigs using CLC Genomics Workbench 11 (Qiagen, USA) and Trinity v2.0.6 (Haas et al., 2013). A contig (4,760 reads, average coverage:73.76) of 6,391 nucleotides was found to share the highest sequence identity (99.83%) with CGMMV isolate GDLZ (MK933286), irrespective of other virus-like contigs related to Polerovirus and Totivirus. Based on the genome of GDLZ isolate, seven specific primers (Table S1) were designed to amplify the full viral genomic sequences using a PrimeScriptTM One-Step RT-PCR Kit. Seven expected amplicons were obtained, cloned, and sequenced. The complete genome was determined to be 6,423 nucleotides (GenBank accession number OR854819) in length and designated as LNMJ isolate. LNMJ shared 96.8%-99.7% nucleotide sequence identities with CGMMV isolates from China. Phylogenetic analysis based on the complete genome sequences showed that LNMJ clustered together with CGMMV isolates hn (GenBank accession number KC851866), GDLZ (GenBank accession number MK933286), and JD8 (GenBank accession number KM873784) from China. The specific primers LM-TJ-3F/3R were designed to determine the virus-symptom association for LNMJ, and all twelve symptomatic C. rostellatum plants collected from fields tested positive for LNMJ. Two out of six randomly selected aphids from the diseased plants also tested positive. To further prove its infectivity, LNMJ was inoculated mechanically onto ten healthy Nicotiana benthamiana plants, and the results indicated a high infection rate of 80% (8/10), at 30 days post-inoculation despite no distinct symptoms observed. To our knowledge, this is the first report of the natural infection of C. rostellatum plants with CGMMV. C. rostellatum is a widespread herb in China (Wei et al., 2019) and more surveys are needed to determine the distribution of CGMMV. The habitats of C. rostellatum span diverse agroecological zones, and thus our study underscores the potential spillover of CGMMV to neighboring crops as a significant risk.