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Antibody-drug conjugates (ADCs) are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies. In this study, we report the generation of a monoclonal antibody against monomethyl auristatin E (MMAE) and the development, validation, and application of sensitive and high-throughput enzyme-linked immunosorbent assays (ELISA) to measure the concentrations of MMAE-conjugated ADCs and total antibodies (tAb, antibodies in ADC plus unconjugated antibodies) in cynomolgus monkey sera. These assays were successfully applied to in vitro plasma stability and pharmacokinetic (PK) studies of SMADC001, an MMAE-conjugated ADC against trophoblast cell surface antigen 2 (TROP-2). The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit, Lys (m-dPEG24)-Cit, and Val-Cit linkers. The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation between serum concentrations and the OD450 values, with R2 at 1.000, and the dynamic range was 0.3–35.0 ng/mL and 0.2–22.0 ng/mL, respectively; the intra- and inter-assay accuracy bias% ranged from −12.2% to −5.2%, precision ranged from −12.4% to −1.4%, and the relative standard deviation (RSD) was less than 6.6% and 8.7%, respectively. The total error was less than 20.4%. The development and validation steps of these two assays fulfilled the acceptance criteria for all addressed validation parameters, which suggested that these can be applied to quantify MMAE-conjugated ADCs, as well as in PK studies. Furthermore, these assays can be easily adopted for development of other similar immunoassays.

Goat is an important sector for meat and dairy products. Diacylglycerol O-acyltransferase 1 (DGAT1), which is a key gene in milk production, has been recently detected to overlap with a novel copy number variation (CNV) in goats. CNVs could be genetic markers providing new insights into the genetic basis of phenotypic variation. Up to now, there are no reports on the DGAT1-related CNV (DGAT1 CNV) in Chinese goats. This study first detected the distribution of the DGAT1 CNV in Chinese seven goat breeds, finding substantial differences among dairy, meat, and fiber goats (P

Objective To evaluate the clinical outcome of manual reduction combined with pedicle fixation through Wiltse paraspinal approach (WPA) in the treatment of thoracolumbar fractures. Methods From May 2017 to May 2019, 48 thoracolumbar fractures patients without neurological symptoms were enrolled in this study. Forty‐eight patients were randomly divided into two groups based on the different surgical treatment. Group 1 was manual reduction combined with pedicle screw fixation through Wiltse paraspinal approach treatment group. Group 2 was pedicle screw fixation through traditional posterior approach treatment group. The operation time (OT), intraoperative blood loss (BL), postoperative drainage (PD), time of brace (TB) and the cobb angle recovery of the injured kyphosis in the prone position were obtained and compared between the two groups, respectively. Comparison of cobb angle changes, serum creatine kinase (CK) level, pain visual analogue score (VAS), Oswestry disability index (ODI), and multifidus cross‐sectional (MCS) area changes were achieved between the two groups, respectively. Results Forty‐eight patients were enrolled in this study and each group had 24 patients. There was no significant difference between the two groups in patient's age, height, weight, and body mass index (BMI). There were 20 males and four females in group 1. The mean age, height, weight, and BMI of patients were 61.99 ± 11.00 years (range, 42–75 years), 175.21 ± 4.49 cm, 76.71 ± 4.87 kg, and 24.98 ± 1.03 kg/m2 in group 1, respectively. Group 2 had 18 males and six females, and the mean age, height, weight, and BMI of patients were 57.95 ± 9.22 years (range, 44–77 years), 176.37 ± 4.56 cm, 77.42 ± 4.61 kg, and 24.87 ± 1.10 kg/m2 in group 2, respectively. The mean bleeding volume of group 1 was significantly less than group 2 (64.13 ± 9.77 ml and 152.13 ± 10.73 ml, respectively) (P, In this study, the results showed that preoperative manual reduction could help restore the height of injured vertebrae. Wiltse intermuscular approach has less intraoperative blood loss, shorter operation time and paraspinal muscle damage.

Copy number variation (CNV) is one kind of genomic structure variations and presents as gains and losses of genomic fragments. More recently, we have made an atlas of CNV maps for livestock. In the future, it is a primary focus to determine the phenotypic effects of candidate CNVs. Lysine Acetyltransferase 6 A (KAT6A) is a protein coding gene and plays a critical role in many cellular processes. However, the effects of KAT6A CNVs on sheep body measurements remains unknown. In this study, we performed quantitative polymerase chain reaction (qPCR) to detect the presences and distributions of three CNV regions within KAT6A gene in 672 sheep from four Chinese breeds. Association analysis indicated that the three CNVs of KAT6A gene were significantly associated with body measurement(s) in Small-tailed Han sheep (STH) and Hu sheep (HU) (p 0.05) were observed. Additionally, only one CNV was significantly associated with body measurement (body length) in Chaka sheep (CK) (p < 0.05). Our study provided evidence that the CNV(s) of KAT6A gene could be used as candidate marker(s) for molecular breedings of STH, HU, and CK breeds.

The introduction of N2 -fixing species into a Eucalyptus plantation resulted in a successful planting system. It is essential to understand the contribution of nitrogen (N) competition and photosynthetic efficiency to plant dry matter yield to shed more light on the growth mechanism of the Eucalyptus/legume system. We compared N competition, photosynthesis and dry matter yield of Eucalyptus urophylla × E. grandis and the N2 -fixing tree species Dalbergia odorifera in intercropping and monoculture systems under different N levels. The photosynthesis of E. urophylla × E. grandis was improved, while that of D. odorifera was inhibited in the intercropping system. Intercropped E. urophylla × E. grandis increased the N utilization and the dry matter yield by 6.57-48.46% and 7.59-97.26%, and decreased those of D. odorifera by 10.21-30.33% and 0.48-13.19%, respectively. Furthermore, N application enhanced the competitive ability of E. urophylla × E. grandis relative to D. odorifera and changed the N contents and chlorophyll synthesis to optimize the photosynthetic structure of both species. Our results reveal Eucalyptus for photosynthesis, N absorption and increasing the growth benefit from the introduction of N2 -fixing species, which hence can be considered to be an effective sustainable management option of Eucalyptus plantations.

Gossypol has been reported to exhibit antitumor effects against several human cancers. However, the anticancer effects of gossypol on nasopharyngeal carcinoma (NPC) have not been investigated. Against this backdrop, the present study was designed to evaluate the anticancer effects of gossypol against NPC cells and to identify the signaling pathways involved through bioinformatic analysis. Gossypol-inhibited death of NPC cells is concentration-dependent. To explore the underlying mechanism for gossypol's antitumor effect, microarray of gossypol-treated and -untreated NPC cells was performed. A total of 836 differentially expressing genes (DEGs) were identified in gossypol-treated NPC cells, of which 461 genes were upregulated and 375 genes were downregulated. The cellular components, molecular functions, biological processes, and signal pathways, in which the DEGs were involved, were identified by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The Gene Set Enrichment Analysis (GSEA) predicted upstream transcription factors (TF) ETS2 and E2F1 that regulate DEGs. Weighted Gene Co-expression Network Analysis (WGCNA) was performed to identify a class of modules and genes related to DNA repair and cell cycle. TNFRSF10B, a receptor for death in NPC cells, was knocked down. The results suggested that the ability of NPC cells to resist gossypol killing was enhanced. In addition, to further investigate the possible molecular mechanisms, we constructed a transcriptional regulatory network of TNFRSF10B containing 109 miRNAs and 47 TFs. Taken together, our results demonstrated that gossypol triggered antitumor effects against NPC cells, indicating its applicability for the management of NPC.

Accurate measurement of the complex permittivity of plant is essential for remote-sensing applications. The complex dielectric properties of moso bamboo ( Phyllostachys heterocycla ) were measured from 0.5 to 18 GHz based on the coaxial transmission/reflection method. A high-precision numerically controlled machine was used to process the bamboo samples. Based on the measured data, the complex permittivity can be better modeled as a second-order polynomial about the moisture content than the traditional exponential function. The real parts of the relative dielectric permittivity decrease with the increase in the frequency, while the imaginary parts decline first and then rise. The dielectric permittivity of the longitudinal direction is larger than that of the cross-sectional direction due to the anisotropic fibrocyte structure of moso bamboo.

BackgroundTo explore the correlation between visual field (VF) defect values and retinal nerve fiber layer (RNFL) thickness for intracranial tumor and glaucoma patients.MethodsRetrospective analysis is performed for the intracranial and glaucoma patients, whose VF defect values were measured with Octopus perimeter cluster analysis, RNFL thickness, ganglion cell layer (GCL) thickness, and optic disk parameters measured with swept-source OCT. The differences between VF and RNFL (including the data of optic disc) are calculated. The correlation between VF defect values and RNFL and GCL thickness are explored.ResultsIn total 43 eyes of 29 patients with intracranial tumor and 31 eyes of 19 patients with glaucoma were enrolled. The thickness of RNFL not only for the whole (360°), but also for the four quadrants was thinner in the glaucoma group than those of the intracranial tumor group (p). There is no significant difference in VF for those two groups except glaucoma having lower sLV (pConclusionsIntracranial tumor has a weak correlation between the RNFL thickness and Octopus VF MD, compared with that of glaucoma. OCT and Octopus VF might provide more helpful information for the differential diagnosis of intracranial tumor and glaucoma.

Revealing the dynamics of soil organic carbon (Corg) and nutrients at aggregate scales is essential for improving our understanding of soil Corg mitigation and nutrient restitution in the Cunningha...

Background Meniere's disease (MD), characterized by episodic vertigo attacks and fluctuating progressive hearing loss, is treated by low-dose intratympanic gentamicin (ITG) injections. Whether ITG causes hearing loss is controversial, and knowledge about its effects on the contralateral hearing and vestibular function is lacking. Aims/objectives We aimed to evaluate the effect of ITG on bilateral auditory and otolith organ function in patients with unilateral refractory MD. Material and methods The data of 30 patients was collected, including history, and pure tone audiometry and vestibular-evoked myogenic potentials (VEMPs) results before and one month after ITG treatment. Changes in vertigo were assessed at a two-year follow-up. Results One month after ITG injection, auditory thresholds between 125 Hz and 8 kHz on the injection side remained unchanged but have improved on the contralateral side at 125 Hz, 250 Hz, 1 kHz. The cervical and ocular VEMP solicitation rates on the injection side were lower than before the injection. Two years after treatment, vertigo was improved in 88.5% and complete controlled in 76.7% patients respectively. Conclusions and significance The intractable vertigo of MD can be effectively controlled by ITG injection. This can improve the low and medium frequency hearing level in the contralateral ear, suggesting that it might help prevent contralateral MD occurrence.

Circular RNAs (circRNAs) are non-coding RNAs that have attracted considerable attention in recent years. Owing to their distinct circular structure, circRNAs are stable in cells. Autophagy is a catabolic process that helps in the degradation and recycling of harmful or inessential biological macromolecules in cells and enables cells to adapt to stress and changes in the internal and external environments. Evidence has shown that circRNAs influence the course of a disease by regulating autophagy, which indicates that autophagy is involved in the onset and development of various diseases and can affect drug resistance (for example, it affects cisplatin resistance in tumors). In this review, we summarized the role of circRNAs in autophagy and their influence on disease onset and progression as well as drug resistance. The review will expand our understanding of tumors as well as cardiovascular and neurological diseases and also suggest novel therapeutic strategies. Abbreviations: ACR: autophagy-related circRNA; ADSCs: adipogenic mesenchymal stem cells; AMPK: AMP-activated protein kinase; ATG: autophagy related; BCL2: BCL2 apoptosis regulator; BECN1: beclin 1; ceRNA: competing endogenous RNA; circRNA: circular RNA; CMA: chaperone-mediated autophagy; EPCs: endothelial progenitor cells; LE/MVBs: late endosomes/multivesicular bodies; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; NSCLC: non-small cell lung cancer; PDLSCs: periodontal ligament stem cells; PE: phosphatidylethanolamine; PtdIns: phosphatidylinositol; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate 1,2-dipalmitoyl; PTEN: phosphatase and tensin homolog; RBPs: RNA-binding proteins; SiO(2): silicon dioxide; TFEB: transcription factor EB; ULK: unc-51 like autophagy activating kinase 1

DNA methylation could take part in the gene expression and acts an important role in muscle development. In this study, DNA methylation and expression in adipose and muscle tissues were examined at...

The reliable design and prediction of enzyme promiscuity to access transformations not observed in nature remains a long-standing challenge. Herein, we present the first example of an intramolecular stereoselective Stetter reaction catalyzed by benzaldehyde lyase, guided by the rational structure screening of various ThDP-dependent enzymes using molecular dynamics (MD) simulations. After optimization, high productivity (up to 99 %) and stereoselectivity (up to 99:1 e.r.) for this novel enzyme function was achieved.

Background Glucocorticoid treatment is used in children with Graves’ disease (GD) only in cases of exophthalmos. The purpose of this study was to observe the effects of glucocorticoid pulse therapy on thyroid function and thyroid antibodies in children with GD. Methods Twenty children who were treated by intravenous methylprednisolone pulse therapy (MPT) followed by oral prednisolone administration and antithyroid drugs were included in the pulse group. Twenty children who were treated with antithyroid drugs alone were included in the control group. Serum concentrations of free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), and thyrotropin receptor antibodies (TRAb) were recorded at baseline and 10 days, 30 days, and 60 days after treatment. Results Significant differences in FT3, FT4, TSH, TPOAb, TGAb, and TRAb levels were found in the pulse group and the control group from baseline to follow-up time points (all p p = 0.023). However, the level of TRAb rose on the 60th day. For values of TRAb at baseline, 10 days, and 60 days after treatment, there were no significant differences respectively between the pulse group and the control group (all p > 0.05). No significant differences were observed in FT3, FT4, TSH, TPOAb, and TGAb levels between the pulse group and the control group (all p > 0.05). Conclusions The results suggested that the effect of intravenous MPT followed by oral prednisolone on TRAb level was temporary in children with GD. Glucocorticoid pulse therapy was not beneficial for the sustained recovery of thyroid function.

Copy number variation (CNV) is the most prevalent type of genetic structural variation that has been recognized as an important source of phenotypic variation in humans, animals and plants. However, the mechanisms underlying the evolution of CNVs and their function in natural or artificial selection remain unknown. Here, we generated CNV region (CNVR) datasets which were diverged or shared among cattle, goat, and sheep, including 886 individuals from 171 diverse populations. Using 9 environmental factors for genome-wide association study (GWAS), we identified a series of candidate CNVRs, including genes relating to immunity, tick resistance, multi-drug resistance, and muscle development. The number of CNVRs shared between species is significantly higher than expected (P

Atherosclerosis is the main cause of cardiovascular disease. Systemic inflammation is one important characteristic in atherosclerosis. Pro-inflammatory macrophages can secrete inflammatory factors and promote the inflammation of atherosclerosis. It has a great value for the treatment of atherosclerosis by inhibiting the release of inflammatory factors in macrophages. However, the detailed mechanism of this process is still unclear. In this study, we constructed an APOE-/- mice model of atherosclerosis to research the molecular mechanism of atherosclerosis. Protein tyrosine phosphatase non-receptor type 2 (PTPN2), an anti-inflammatory gene, was dramatically decreased in inflammatory mice. Deletion of PTPN2 could significantly induce monocytes toward M1 phenotype of macrophages, enhance the secretion of IL-12 and IL-1, and promote cell proliferation, invasion and metastasis. Mechanism research showed that PTPN2-mediated p65/p38/STAT3 de-phosphorylation could block the process of macrophage inflammation. In vivo experiments showed that PTPN2 may effectively inhibit the inflammatory response during atherosclerosis. In conclusion, we uncovered the negative role of PTPN2 in the occurrence of atherosclerosis, and this study provides a new potential target for atherosclerosis treatment.

The aim of this study was to detect the novel copy number variation (CNV) locus of NCAM2 gene in Chinese Holstein, and to analyze the effect of the novel CNV locus in NCAM2 gene on milk composition...

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide. Metabolic reprogramming has been recognized as a core feature in HCC. In line with this idea, we verified that increased miR‐23a inhibited STAT5A expression and promoted glucose metabolism through activated AKT phosphorylation in HCC. This new signaling pathway may offer new treatment target for HCC patients., Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Here, we identified that increased miR‐23a expression in HCC tissues was associated with worse survival. More importantly, we found that STAT5A was a target of miR‐23a, whose levels significantly decreased in tumor tissues. Stable expression of STAT5A in Huh7 cells suppressed glucose metabolism and tumor growth. Finally, this study showed that increased miR‐23a negatively regulated STAT5A, which further activated AKT signaling to enable rapid metabolism for accelerated tumor growth in HCC. Taken together, our results demonstrated that the miR‐23a‐STAT5A‐AKT signaling pathway is critical to alter glucose metabolism in HCC and may offer new opportunities for effective therapy.

Circular RNAs (circRNAs) play an essential role in tumorigenesis and development. However, they have rarely been investigated in nasopharyngeal carcinoma (NPC). This study aimed to investigate the role of circRNA in the invasion and metastasis of NPC. We screened and verified the high expression of circSETD3 in NPC cell lines using RNA sequencing (RNA-Seq) and verified the results of NPC biopsy samples using real-time quantitative polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). In vivo and in vitro experiments indicated that circSETD3 could promote NPC cell invasion and migration. We compared the proteomic data of NPC cells before and after the overexpression or knockdown of circSETD3 in combination with bioinformatics prediction and experimental verification. It was found that circSETD3 competitively adsorbs to miR-615-5p and miR-1538 and negates their inhibitory effect on MAPRE1 mRNA, thereby upregulating the expression of MAPRE1. The upregulated MAPRE1 then inhibits the acetylation of α-tubulin, promotes the dynamic assembly of microtubules, and enhances the invasion and migration capabilities of NPC cells. The results of this study suggest that circSETD3 is a novel molecular marker and a potential target for NPC diagnosis and treatment.

Growing evidence indicates that the non-coding 3'-untranslated region (3'UTR) of genes acts as competing endogenous RNAs (ceRNAs) to exert their roles in a number of diseases, including cancer. In the present study, MMP1 messenger RNA was identified to be significantly up-regulated in oral squamous cell carcinoma (OSCC) tissues, and both MMP1 and its 3'UTR promoted tumor growth and cell motility. Further mechanism investigations indicated that MMP1 3'UTR was able to antagonize miR-188-5p; in addition, overexpression of MMP1 3'UTR up-regulated the expression level of SOX4 and CDK4, target genes of miR-188-5p, which have also been identified as oncogenic driver genes in OSCC. Therefore, a ceRNA regulatory network among MMP1, SOX4, and CDK4 mediated via competing for binding to miR-188-5p was proved. Taken together, the present study demonstrates for the first time that MMP1 mRNA participates in the development of OSCC via ceRNA regulatory mechanism and genes involved in the ceRNA network may provide a novel avenue for target therapy.

Soybean cyst nematode (SCN, Heterodera glycines) is a chief plant–parasitic nematode of soybean. Application of synthetic chemical nematicides poses negative side effects to human health and the environment. Therefore, the search for a safe and effective approach is more relevant. This study evaluated the effects of Genistein and Daidzein on the physiological index of soybean cyst nematodes, individual morphology, reversal frequency, respiration, and body fluid leaking of second–stage juveniles (J2s) of soybean cyst nematode. The results showed that body length of J2s decreased, while stylet and tail transparent area elongated. Additionally, after the treatment, the body became hollow and shrunken, the J2s stiffened, whereas the reversal frequency decreased dramatically after 24 h of treatment. Moreover, the body fluid leakage was intensified and respiration was inhibited. Oxygen consumption decreased by 86.7 % and 70.1 %, while, in contrast, electrical conductivity increased by 40.1 % and 36 % at 100 μg mL−1 of Genistein and Daidzein, respectively, after 48 h of exposure. The smaller number of J2s in soybean roots, the slower development rate, and the abnormal sexual differentiation were found in greenhouse assay. Thus, Genistein and Daidzein, especially Genistein, have strong effects on the physiological index of soybean cyst nematodes. Moreover, the effects were time and dosage–dependent.

Sulfane sulfur activates actinorhodin production and sporulation in Streptomyces coelicolor. A gene cluster controlling intracellular sulfane sulfur levels is identified. Genetically modifying this gene cluster can change sulfane sulfur levels, thereby altering the actinorhodin production and sporulation., Summary Sulfane sulfur, including polysulfide and persulfide, is a newly identified cellular component present in microorganisms; however, its physiological functions are unclear. Streptomyces coelicolor M145 is a model strain of actinomycetes, which produces several polyketides, including actinorhodin. Herein, we found that both exogenously added and endogenously generated sulfane sulfur increased the actinorhodin production and accelerated spore formation of S. coelicolor M145. This bacterial species carries a natural gene circuit containing four genes that encode a CsoR‐like transcription factor (ScCsoR), persulfide dioxygenase (ScPDO), rhodanese and a sulfite transporter, which were shown to be responsible for sensing and removal of excessive sulfane sulfur. ScCsoR was observed to bind to the promoters of the four genes, thus repressing their transcription. Sulfane sulfur modified Cys37 of ScCsoR, and the modified ScCSoR did not bind to the promoters, thereby activating the transcription of ScPDO. The deletion of ScCsoR decreased cellular sulfane sulfur, while the deletion of ScPDO increased its levels. The increased sulfane sulfur promoted actinorhodin production and sporulation. This study unveiled a natural gene circuit for maintaining sulfane sulfur homeostasis in bacteria. Further, we identified the trigger effect of sulfane sulfur on actinorhodin production, presenting a new approach for activating polyketide gene clusters in actinomycetes.

European taurine and East Asian taurine are two main clades in Bos taurus, but their genomic differences are not clearly elucidated. Here, we sequenced 16 Mongolian cattle genomes and compared them to the 92 genomes of 10 representative breeds worldwide. We found the highest LD level in Mishima cattle and the fastest LD decay in European taurine. Phylogenetic analysis revealed that Mongolian, Hanwoo and Mishima cattle were clustered into East Asian taurine. From selective sweep, gene annotation, functional enrichment and differential expression analysis, we identified selective signals including genes and/or pathways related to rapid growth and large body size in European taurine, and superior meat quality in East Asian taurine. Our findings will help us understand the evolutionary history and formation process of the breeds and provide theoretical materials regarding the genetic mechanism underlying breed characteristics and molecular breeding programmes of the taurine clades in the future.

This study developed an innovative process for the treatment of low-ammonium wastewater in a single-stage bioreactor over 250 days. Partial nitritation-anammox and partial denitritation-anammox (PN/A-PDN/A) processes were combined under aerobic/anoxic operation, and a high nitrogen removal efficiency (94.6%) was obtained at a nitrogen removal rate of 0.54 kg N m-3 d-1 and a chemical oxygen demand to total inorganic nitrogen (COD/TIN) ratio of 0.28. Mass balance analysis identified anammox as the dominant nitrogen removal pathway, achieving 88.3% nitrogen loss. The abundance of anammox bacteria and their bioactivity rapidly increased and were effectively maintained, as indicated by qPCR and bioactivity tests. The PN/A-PDN/A process provided two pathways of nitrite production for anammox, which favored the enrichment of anammox bacteria and stable processing. In addition, the enrichment of anammox bacteria was promoted by selective floc discharge since anammox bacteria are mainly located in granules (relative abundance of 29.64 ± 7.89%). Competitive organisms (including heterotrophic bacteria and nitrite oxidizing bacteria), enriched in flocs, were washed out. Overall, these findings confirmed anammox, sequentially combined with PN and PDN via aerobic/anoxic strategy, as a promising alternative for mainstream anammox.

Max dimerization protein 3 (MXD3) belongs to the MYC superfamily of basic helix‐loop‐helix leucine zipper transcription factors, and MXD3‐MAX heterodimers can bind to promoters of target genes to modulate their expression. The aim of this study was to determine the MXD3 mRNA expression levels in various cattle tissues comprising heart, liver, spleen, lung, kidney, Longissimus dorsi muscle and subcutaneous fat in Chinese Qinchuan and Xianan cattle breeds. The RT‐qPCR data showed that the MXD3 gene was variably expressed between all tissues and at levels that were significantly different between two breeds (p T and g.3801 T>C) and one SNP in 3′untranslated region (3′UTR) (g.6263 G>A) of MXD3 gene. Association analysis revealed strong associations between pairwise and triple SNP combinations and the growth traits. Based on these results, we suggest that MXD3 polymorphisms could be useful as molecular markers in the Chinese beef cattle breeding program., Three single‐nucleotide polymorphisms in MXD3 and its expression level in various tissues of cattle.

Copy number variation mainly refers to the copy number change of DNA fragments from 1 to 5 Mb. The deletion, duplication, inversion and ectopic of these fragments are collectively referred to as CN...

Copy number variations (CNVs) were similar to single nucleotide polymorphisms (SNPs) and insertion-deletion (InDel), regarded as genetic variations in many species. CNV is defined as the variable change of DNA segment length compared with the reference genome, including gains or losses from 50 bp to several mega bases. The functions of USP16 gene are diverse, such as regulating the cell cycle, DNA damage, histone H2A deubiquitination or mitotic nuclear division. To analyze the relationship between CNV of USP16 gene and milk traits in Chinese Holstein, we used qPCR to detect the individuals of Chinese Holstein (n = 180). The results showed that the effect of USP16 gene CNV on daily milk yield and fat percentage had significant difference (p < 0.05). The gain was the advantage type in daily milk yield and the loss was the advantage type in fat percentage. Therefore, CNV of USP16 gene is an important factor of milk traits in Chinese Holstein. Meanwhile, it may be used as a molecular marker for assisted selection of milk traits in Chinese Holstein, which provides a theoretical basis for the genetic improvement of cow breeds in China.

Metabolic reprogramming is a core hallmark of cancer but it remains poorly defined in hepatocellular carcinogenesis (HCC). Here we show that hepatic aldolase B (Aldob) suppresses HCC by directly binding and inhibiting the rate-limiting enzyme in the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PD). A stage-dependent decrease of Aldob and increase of G6PD in human tumors are correlated with poor prognosis for patients with HCC. Global or liver-specific Aldob knockout promotes tumorigenesis in mice through enhancing G6PD activity and pentose phosphate pathway metabolism, whereas pharmacological inhibition or genetic knockdown of G6PD suppresses HCC. Consistently, restoration of Aldob in Aldob knockout mice attenuates tumorigenesis. We further demonstrate that Aldob potentiates p53-mediated inhibition of G6PD in an Aldob–G6PD–p53 complex. This scaffolding effect is independent of Aldob enzymatic activity. Together, our study reveals a new mode of metabolic reprogramming in HCC due to the loss of Aldob, suggesting a potential therapeutic strategy for HCC treatment. Yin and colleagues show that hepatic aldolase B suppresses hepatocellular carcinoma by controlling tumor metabolic reprogramming through G6PD inhibition.

The simultaneous chemical phosphorus removal (SCPR) process has been widely applied in wastewater treatment plants (WWTPs) due to the high phosphorus removal efficiency through the synergy of biological and chemical phosphorus removal (BPR and CPR). However, phosphorus removal reagents could affect the bacterial community structure in the SCPR system and further affect the BPR process. The BPR phenotypes and community structures in the SCPR system, especially the population of polyphosphate-accumulating organisms (PAOs), are not completely clear. In order to clarify these problems, the phosphorus removal performance and the PAO population in a full-scale SCPR system were investigated. Results showed that diverse PAOs still existed in the SCPR system though the BPR phenotypes were not observed. However, the relative abundances of Accumulibacter and Tetrasphaera, the two most important genera of PAOs, were only 0.59% and 0.20%, respectively, while the relative abundances of Competibacter and Defluviicoccus, two genera of glycogen-accumulating organisms (GAOs), were as high as 5.77% and 1.28%, respectively. Batch tests showed that PAOs in the SCPR system still had a certain polyphosphate accumulating metabolic activity, which could gradually recover after stopping the addition of chemical reagents. This study provided a microbiological basis for the SCPR system to recover the enhanced biological phosphorus removal (EBPR) performance under suitable conditions, which could reduce the dosage of chemical reagents and the operational cost.

Copy number variations are primary source of genetic variations, which are associated with essential traits in many organisms. During recent years, there have been numerous research works that reveal functions of CNV. However, these studies provide only several references about copy number variations in the sheep genome. In this study, we examined the copy number variation of the TOP2B gene in three Chinese sheep breeds (Chaka sheep, Hu sheep, Small-tailed Han sheep) and performed correlation analysis with growth traits, to detect the influence of CNVs. TOP2B copy numbers were divided into three distribution groups (gain, median, loss) in three Chinese sheep breeds. The distribution amount of copy number < 2 of TOP2B CNVs was dominant in all sheep breeds. The statistical analysis showed that TOP2B CNV had a significant effect on body length in CK sheep (p < 0.05), and effects on chest circumference, canon circumference (p < 0.05) in HU sheep. CNVs in STH sheep breed were relevant to chest circumference and height of hip cross (p < 0.05). These results confirmed the relationship between CNV of TOP2B gene and growth traits in three sheep breeds, and provide a reliable reference for sheep breeding.

Hypersaline lakes and saltern areas are important industrial and biodiversity resources in the Qaidam Basin of China that reside at > 2600 m asl. Most hypersaline environments in this area are characterized by saturated salinity (~ 300 g/L salinity), nearly neutral pH, intense ultraviolet radiation, and extremely variable temperature fluctuations. The core bacterial communities associated with these stressful environments have nevertheless remained uninvestigated. 16S rRNA gene Illumina sequencing analyses revealed that the bacterial communities were dominated by core lineages including the Proteobacteria (39.4–64.6%) and the Firmicutes (17.0–42.7%). However, the relative abundances of common lineages, and especially the five most abundant taxa of Pseudomonas, Lactococcus, Anoxybacillus, Acinetobacter, and Brevundimonas, were highly variable across communities and closely associated with hypersaline characteristics in the samples. Network analysis revealed the presence of co-occurrence high relative abundance taxa (cluster I) that were highly correlated across all hypersaline samples. Additionally, temperature, total organic carbon, K+, and Mg2+ correlated highest with taxonomic distributions across communities. These results highlight the potential mechanisms that could underlie survival and adaptation to these extreme hypersaline ecosystems.

Adipose development is regulated by a series of complex processes, and non-coding RNAs (ncRNAs), including circular RNAs (circRNAs), play important roles in regulating proliferation and differentiation of adipocytes. In this study, we profiled circRNA expression in cattle fat tissue during calf and adult developmental stages and detected 14,274 circRNA candidates. Some circRNAs are differentially expressed between two developmental stages. We characterized circFUT10, named for its host gene FUT10, a highly expressed and abundant circRNA. Luciferase screening, an RNA-binding protein immunoprecipitation (RIP) assay, quantitative real-time PCR, and western blotting assays indicated that circFUT10 directly binds let-7c/let-e, and PPARGC1B (peroxisome proliferator-activated receptor γ coactivator 1-β) is identified as a target of let-7c. Flow cytometry, EdU (5-ethynyl-2′-deoxyuridine) incorporation, a CCK-8 (cell counting kit-8) assay, oil red O staining, and western blotting assays demonstrated that circFUT10 promotes adipocyte proliferation and inhibits cell differentiation by sponging let-7c. The results demonstrate that circFUT10 binding of let-7c promotes cell proliferation and inhibits cell differentiation by targeting PPARGC1B in cattle adipocytes., Graphical Abstract, In order to verify the potential function of circRNA in adipose tissue, high-throughput sequencing of Qinchuan subcutaneous adipose tissue was performed, and circFUT10 was differentially expressed in calf and adult cattle adipose tissue. Experimental verification showed that circFUT10 promoted the proliferation of adipose cells and inhibited their differentiation by combining with let-7 family members.

Reticuloendotheliosis virus (REV) is an avian retrovirus that causes an oncogenic, immunosuppressive, and runting-stunting syndrome in avian hosts. The co-infection of REV and Marek’s disease virus (MDV), an oncogenic herpesvirus in chickens, further increases disease severity and reduces MDV vaccine efficacy. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has successfully been used against pathogens in mammalian cells. However, the large size of the CRISPR-Cas9 coding sequences makes its in vivo delivery challenging. Here, following the design of a panel of single-guided RNAs targeting REV, we demonstrate that CRISPR/Cas9 can efficiently mediate the editing of the long terminal repeats of REV, resulting in the inhibition of viral protein expression. The CRISPR-Cas9 system disrupts the integrated proviral genome and provides defense against new viral infection and replication in chicken cells. Moreover, by constructing recombinant MDV carrying CRISPR-Cas9 components using an attenuated MDV vaccine strain as the vector, we efficiently delivered the CRISPR-Cas9 system into chickens, and the MDV-delivered CRISPR-Cas9 drastically reduced REV viral load and significantly diminished REV-associated symptoms. To our knowledge, this is the first study establishing avian retrovirus resistance in chickens utilizing herpesvirus-delivered CRISPR-Cas9, which provides a novel and effective strategy against viral infections., Graphical Abstract, The CRISPR-Cas9 system has successfully been used against pathogens in mammalian cells. However, the large size of the CRISPR-Cas9 coding sequences makes its in vivo delivery challenging. This study established avian retrovirus resistance in chickens utilizing herpesvirus-delivered CRISPR-Cas9, which provides a novel and effective strategy against viral infections.

Introduction The Polycomb group (PcG) is an important family of transcriptional regulators that controls growth and tumorigenesis. The PcG mainly consists of two complexes, PRC1 and Polycomb Repressive Complex 2 (PRC2). Polycomb-like 2 (PCL2) is known to interact with the PRC2 protein. The role of PCL2 in the development and progression of glioma is unclear. Methods We use The Cancer Genome Atlas (TCGA) database to detect the expression of PCL2 in various tumors. 117 cases of clinical glioma (WHOI–IV) were collected, and PCL2 expression and localization were detected by immunohistochemical staining. Glioma cells U87/U251 were infected with overexpressed and interfered PCL2. CCK8 assay, colony formation assay, EdU method, cell cycle and apoptosis were used to detect cell proliferation and apoptosis. Western blot was used to detect the expression of PRC2-related core proteins. After DZNeP intervention, PRC2 protein expression was again measured to discuss the mechanism of PCL2 action. Results TCGA database results and immunohistochemical staining results suggest that PCL2 is highly expressed in gliomas. We found that the PCL2 gene promoted tumor cell proliferation, enhanced the colony formation ability, and increased S phase in the cell cycle. The overexpression of PCL2 upregulated the expression levels of EZH2 and EED (two core members of PRC2), decreased the expression of SUZ12, increased the level of H3K27 trimethylation (H3K27me3), H3K4 dimethylation (H3K4me2), and decreased H3K9 dimethylation (H3K9me2). The result after interfering with PCL2 was the opposite. Conclusions As an important accessory protein of PRC2, PCL2 can not only change the expression of PRC2 components, but also affect the expression level of Histone methylation. Therefore, PCL2 may be an important hub for regulating the synergy among PRC2 members. This study revealed PCL2 as a new target for tumor research and open up a new avenue for future research in glioma.

DNA methylation, which can affect the expression level of genes, is one of the most vital epigenetic modifications in mammals. Fibroblast growth factor receptor 1 (FGFR1) plays an important role in muscle development; however, DNA methylation of the FGFR1 promoter has not been studied to date in cattle. Our study focused on methylation of the FGFR1 promoter and its effect on bovine myoblast proliferation and differentiation. We identified the FGFR1 core promoter by using luciferase reporter assays; we then studied FGFR1 expression by reverse transcription quantitative polymerase chain reaction, and the methylation pattern in the FGFR1 core promoter by bisulfite sequencing polymerase chain reaction in bovine muscle tissue at three different developmental stages. We used RNAi strategy to investigate the function of FGFR1 in myoblast proliferation and differentiation. Results showed that the FGFR1 core promoters were located at the R2 (-509 to ~-202 bp) and R4 (-1295 to ~-794 bp) regions upstream of the FGFR1 gene. FGFR1 expression level was negatively associated with the degree of methylation of the FGFR1 core promoter during the developmental process. In addition, we found that FGFR1 can promote myoblast proliferation, but had no effect on myoblast differentiation. In conclusion, our results suggest that FGFR1 can promote myoblast proliferation and its transcription can be regulated by the methylation level of the core promoter. Our findings provide a mechanistic basis for the improvement of animal breeding.

Commercial or clinical tissue adhesives are currently limited due to their weak bonding strength on wet biological tissue surface, low biological compatibility, and slow adhesion formation. Although catechol-modified hyaluronic acid (HA) adhesives are developed, they suffer from limitations: insufficient adhesiveness and overfast degradation, attributed to low substitution of catechol groups. In this study, we demonstrate a simple and efficient strategy to prepare mussel-inspired HA hydrogel adhesives with improved degree of substitution of catechol groups. Because of the significantly increased grafting ratio of catechol groups, dopamine-conjugated dialdehyde-HA (DAHA) hydrogels exhibit excellent tissue adhesion performance (i.e., adhesive strength of 90.0 ± 6.7 kPa), which are significantly higher than those found in dopamine-conjugated HA hydrogels (∼10 kPa), photo-cross-linkable HA hydrogels (∼13 kPa), or commercially available fibrin glues (2-40 kPa). At the same time, their maximum adhesion energy is 384.6 ± 26.0 J m-2, which also is 40-400-fold, 2-40-fold, and ∼8-fold higher than those of the mussel-based adhesive, cyanoacrylate, and fibrin glues, respectively. Moreover, the hydrogels can gel rapidly within 60 s and have a tunable degradation suitable for tissue regeneration. Together with their cytocompatibility and good cell adhesion, they are promising materials as new biological adhesives.

In this paper, a step-by-step classification algorithm based on double-layer SVM model is constructed to predict the secondary structure of proteins. The most important feature of this algorithm is to improve the prediction accuracy of α+β and α/β classes through transforming the prediction of two classes of proteins, α+β and α/β classes, with low accuracy in the past, into the prediction of all-α and all-β classes with high accuracy. A widely-used dataset, 25PDB dataset with sequence similarity lower than 40%, is used to evaluate this method. The results show that this method has good performance, and on the basis of ensuring the accuracy of other three structural classes of proteins, the accuracy of α+β class proteins is improved significantly.

Copy number variation (CNV) as an important source of genetic phenotypic and variation is related to complex phenotypic traits. The aim of this study was to investigate the potential associations o...

Phytoremediation is a cost-effective and environment-friendly strategy for decontaminating heavy-metal-contaminated soil. However, the practical use of phytoremediation is constrained by the low biomass of plants and low bioavailability of heavy metals in soil. A pot experiment was conducted to investigate the effects of the metal chelator ethylenediaminetetraacetic acid (EDTA) and EDTA in combination with plant growth-promoting rhizobacteria (Burkholderia sp. D54 or Burkholderia sp. D416) on the growth and metal uptake of the hyperaccumulator Sedum alfredii Hance. According to the results, EDTA application decreased shoot and root biomass by 50% and 43%, respectively. The soil respiration and Cd, Pb, Zn uptake were depressed, while the photosynthetic rate, glutathione and phytochelatin (PC) contents were increased by EDTA application. Interestingly, Burkholderia sp. D54 and Burkholderia sp. D416 inoculation significantly relieved the inhibitory effects of EDTA on plant growth and soil respiration. Compared with the control, EDTA + D416 treatment increased the Cd concentration in shoots and decreased the Pb concentration in shoots and roots, but did not change the Zn concentration in S. alfredii plants. Furthermore, EDTA, EDTA + D54 and EDTA + D416 application increased the cysteine and PC contents in S. alfredii (p 0.05); among all tested PCs, the most abundant species was PC2, and compared with the control, the PC2 content was increased by 371.0%, 1158.6% and 815.6%, respectively. These results will provide some insights into the practical use of EDTA and PGPR in the phytoremediation of heavy-metal-contaminated soil by S. alfredii.

SPARC is a cysteine-rich acidic secreted protein. It is a non-collagen component of bone, which is widely distributed in humans and animals and plays an important role. SPARC has been found in a variety of human cancers (breast cancer, stomach cancer, ovarian cancer, etc.) and diabetes-related research. Especially the muscle and fat metabolism are closely related. In this study, we used a DNA pool to detect a new SNP site (g.12454T > C). A total of 616 samples of four breeds of Qinchuan cattle (QC, n=176), Xianan cattle (XN, n=160), Pinan cattle (PN, n=136) and Jiaxian cattle (JX, n=144) were analyzed and identified with ARMS-PCR. In addition, we correlated SNP with growth traits and showed significant correlation with growth traits such as rump length, hip width, and body length (p

The objective of this study was to establish a real-time LAMP assay for authentication of rape (Brassica napus) honey to protect consumers from commercial honey adulteration. The LAMP primers targeting the internal transcribed spacer (ITS) of Brassica napus were designed, and its specificity was tested. The LAMP reaction temperature was also optimized, and the detection limit of the LAMP assay was determined with a serial dilution of genomic DNA from the seeds of Brassica napus. The results showed that the real-time LAMP assay can accurately and specifically detect the rape component in honey, and the detection limit was 10 pg genomic DNA of Brassica napus. Data on monofloral honey samples indicate that the real-time LAMP assay was 100% in concordance with the reported TaqManTM PCR assay. This study provides a promising solution for facilitating the authentication of rape honey in food retail market.

Cardiovascular diseases (CVD), including ischemic heart diseases and cerebrovascular diseases, are the leading causes of morbidity and mortality worldwide. Atherosclerosis is the major underlying factor for most CVD. It is well-established that oxidative stress and inflammation are two major mechanisms leading to atherosclerosis. Under oxidative stress, polyunsaturated fatty acids (PUFA)-containing phospholipids and cholesterol esters in cellular membrane and lipoproteins can be readily oxidized through a free radical-induced lipid peroxidation (LPO) process to form a complex mixture of oxidation products. Overwhelming evidence demonstrates that these oxidized lipids are actively involved in the inflammatory responses in atherosclerosis by interacting with immune cells (such as macrophages) and endothelial cells. In addition to lipid lowering in the prevention and treatment of atherosclerotic CVD, targeting chronic inflammation has been entering the medical realm. Clinical trials are under way to lower the lipoprotein (a) (Lp(a)) and its associated oxidized phospholipids, which will provide clinical evidence that targeting inflammation caused by oxidized lipids is a viable approach for CVD. In this review, we aim to give an update on our understanding of the free radical oxidation of LPO, analytical technique to analyze the oxidation products, especially the oxidized phospholipids and cholesterol esters in low density lipoproteins (LDL), and focusing on the experimental and clinical evidence on the role of lipid oxidation in the inflammatory responses associated with CVD, including myocardial infarction and calcific aortic valve stenosis. The challenges and future directions in understanding the role of LPO in CVD will also be discussed.

CKLF-like MARVEL transmembrane domain-containing 2 (CMTM2) plays an important role in animal reproduction, and abnormal CMTM2 expression leads to spermatogenesis disorders. This study was conducted to assess the role of CMTM2 in goat reproduction by investigating an insertion/deletion (indel) variation and its effect on litter size, and to reveal its functional mechanism. A 14-base pair (bp) indel was found at position -861 to -848 nt of the CMTM2 promoter in 1131 female Shaanbei white cashmere goats. Association analyses revealed that the 14-bp indel in dams was significantly correlated with the size of the first litter (P = 0.013), with the 14-bp deletion significantly decreasing litter size. Moreover, litter size at first kidding was significantly correlated with genotype frequencies (P = 0.019). Expression of the goat CMTM2 gene was detected in testes and ovaries. In male, CMTM2 was increased after the initiation of meiosis in the developing testis. In female, CMTM2 expression was higher in ovary from multiple prolific goats at first kidding compared to non-prolific goats. Moreover, both in testis after initiation of meiosis and in ovary, the homozygous 14-bp inserted genotype II was associated with increased CMTM2 expression compared to the heterozygous genotype ID (P 0.05). To further explore whether the 14-bp indel was located in the core promoter activity region of the CMTM2 promoter, the five recombinant plasmids pGL3-pro1 (-1756 to +83), pGL3-pro2 (-1200 to +83), pGL3-pro3 (-763 to +83), pGL3-pro4 (-496 to +83), and pGL3-pro5 (-205 to +83) were co-transfected with pRL-TK into HEK293T and GC-1 cells. A luciferase reporter assay showed that the pGL3-pro2 and pGL3-pro5 vectors produced significantly stronger luminescence than the other vectors. Interestingly, the 14-bp indel locus was included in the pGL3-pro2 plasmid, suggesting that the indel was functional. Subsequently, the two recombinant plasmids pGL3-pro2-inserted-allele and pGL3-pro2-deleted-allele were co-transfected with pRL-TK into HEK293T and GC-1 cells, respectively. The luciferase reporter assay demonstrated that the deleted allele of CMTM2 showed significantly lower luminescence activity than the inserted allele (P 0.05), which corresponded to a decrease in litter size in the deletion-deletion genotype. Therefore, our results suggest that a 14-bp deletion in the promoter region of CMTM2 is significantly correlated with litter size in goats; this marker seems promising for breeding selection for improving economically important traits in goats.

Copy number variations (CNVs) are gains and losses of genomic sequence of more than 50 bp between two individuals of a species. Also, CNV is considered to be one of the main elements affecting the phenotypic diversity and evolutionary adaptation of animals. ORMDL sphingolipid biosynthesis regulator 1 (ORMDL1) is a protein-coding gene associated with diseases and development. In our study, the polymorphism of ORMDL1 gene copy numbers in four Chinese sheep breeds (abbreviated CK, HU, STH, and LTH) was detected. In addition, we analyzed the transcriptional expression level of ORMDL1 gene in different tissues of sheep and examined the association of ORMDL1 CNV with growth traits. The statistical analysis revealed that ORMDL1 CNV was remarkably correlated with body height, heart girth, and circumference of cannon bone in HU sheep (P

Anaerobic ammonium oxidation coupled with partial nitritation is critical for cleaner production in sewage treatment. The long-term effects of high- and low-strength influent ammonium (NH 4 + -N) on the anammox activity, ecological niche characteristics and active microbial community were investigated in a one-stage partial nitritation/anammox (PN/A) process. The total nitrogen (TN) removal efficiency was up to 90% with influent NH 4 + -N of 192 mg/L. The 15 N-isotope pairing technique illustrated that the potential anammox rate could reach to 3507.8 nmoL/g-sludge/h, accounting for 73.2% of dinitrogen production. As the influent NH 4 + -N decreased to 63 mg/L, the anammox population significantly decreased and the Nitrospira became the dominant specialized species in the PN/A system. The Nitrobacter had the smallest niche overlap value and the furthest ecological distance to the anammox bacteria among the seven investigated nitrogen conversion-related genes along the influent NH 4 + -N concentration gradient, indicating different ecological similarities. The redundancy analysis showed that the rise of dissolved oxygen caused by low NH 4 + -N might be the main cause of the excessive proliferation of the Nitrospira . The 15 N-DNA-stable isotope probing illustrated that both the class Anaerolineae and Proteobacteria had closely symbiotic relations with the Planctomycetacia in this in situ surveys. This study provides a deep understanding of PN/A process treating low-ammonium mainstream wastewater from the viewpoint of microecology.

Flowering is central to the transformation of plants from vegetative growth to reproductive growth. The circadian clock system enables plants to sense the changes in the external environment and to modify the growth and development process at an appropriate time. Photoperiod-1 (Ppd-1), which is controlled by the output signal of the circadian clock, has played an important role in the wheat “Green Revolution.” In the current study, we systematically studied the relationship between Ppd-1 haplotypes and both wheat yield- and quality-related traits, using genome-wide association analysis and transgenic strategies, and found that highly appropriate haplotypes had been selected in the wheat breeding programs. Genome-wide association analysis showed that Ppd-1 is associated with significant differences in yield-related traits in wheat, including spike length (SL), heading date (HD), plant height (PH), and thousand-grain weight (TGW). Ppd-1-Hapl-A1 showed increased SL by 4.72–5.93%, whereas Ppd-1-Hapl-B1 and Ppd-1-Hapl-D1 displayed earlier HD by 0.58–0.75 and 1.24–2.93%, respectively, decreased PH by 5.64–13.08 and 13.62–27.30%, respectively, and increased TGW by 4.89–10.94 and 11.12–21.45%, respectively. Furthermore, the constitutive expression of the Ppd-D1 gene in rice significantly delayed heading date and resulted in reduced plant height, thousand-grain weight, grain width (GW), and total protein content. With reference to 40years of data from Chinese wheat breeding, it was found that the appropriate haplotypes Ppd-1-Hapl-A1, Ppd-1-Hapl-B1, and Ppd-1-Hapl-D1 had all been subjected to directional selection, and that their distribution frequencies had increased from 26.09, 60.00, and 52.00% in landraces to 42.55, 93.62, and 96.23% in wheat cultivars developed in the 2010s. A Ppd-B1 methylation molecular marker was also developed to assist molecular wheat breeding. This research is of significance for fully exploring the function of the Ppd-1 gene and its genetic resource diversity, to effectively use the most appropriate haplotypes and to improve crop yield and sustainability.

Mitochondrial dysfunction is related to common age-related disorders, including neurodegenerative diseases, metabolic syndrome, and carcinogenesis. Therefore, maintaining the functionality and integrity of mitochondria is important for human health. Herein, we found that sulfide:quinone oxidoreductase (Sqr), which oxidizes hydrogen sulfide to reactive sulfur species (RSS), was indispensable to mitochondria health in the eukaryotic model microorganism Schizosaccharomyces pombe. Sqr knock-out led to morphological changes and functional deficiencies of mitochondria and apoptosis in S. pombe. The Sqr knock-out strain displayed the same phenotypes as the cysteine-synthesis-deficient strain, and cysteine addition complemented the effects caused by Sqr knock-out. In S. pombe, Sqr was the main RSS producer in mitochondria, and RSS instead of H2S was used by cysteine synthase to synthesize cysteine. This finding rewrites the cysteine biosynthesis route in S. pombe and may also in other eukaryotes and prokaryotes, and highlights the importance of cysteine and RSS in maintaining mitochondrial health., Highlights • Sqr is an important RSS producer in mitochondria. • RSS is involved in cysteine de novo biosynthesis. It is the de facto substrate of cysteine synthase. • Sqr is required for maintaining the health of mitochondria, might be a new target for inhibiting cell proliferation.