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Abstract Background Rickettsia and related diseases have been identified as significant global public health threats. This study involved comprehensive field and systematic investigations of various rickettsial organisms in Yunnan Province. Methods Between May 18, 2011 and November 23, 2020, field investigations were conducted across 42 counties in Yunnan Province, China, encompassing small mammals, livestock, and ticks. Preliminary screenings for Rickettsiales involved amplifying the 16S rRNA genes, along with additional genus- or species-specific genes, which were subsequently confirmed through sequencing results. Sequence comparisons were carried out using the Basic Local Alignment Search Tool (BLAST). Phylogenetic relationships were analyzed using the default parameters in the Molecular Evolutionary Genetics Analysis (MEGA) program. The chi-squared test was used to assess the diversities and component ratios of rickettsial agents across various parameters. Results A total of 7964 samples were collected from small mammals, livestock, and ticks through Yunnan Province and submitted for screening for rickettsial organisms. Sixteen rickettsial species from the genera Rickettsia, Anaplasma, Ehrlichia, Neoehrlichia, and Wolbachia were detected, with an overall prevalence of 14.72%. Among these, 11 species were identified as pathogens or potential pathogens to humans and livestock. Specifically, 10 rickettsial organisms were widely found in 42.11% (24 out of 57) of small mammal species. High prevalence was observed in Dremomys samples at 5.60%, in samples from regions with latitudes above 4000 m or alpine meadows, and in those obtained from Yuanmou County. Anaplasma phagocytophilum and Candidatus Neoehrlichia mikurensis were broadly infecting multiple genera of animal hosts. In contrast, the small mammal genera Neodon, Dremomys, Ochotona, Anourosorex, and Mus were carrying individually specific rickettsial agents, indicating host tropism. There were 13 rickettsial species detected in 57.14% (8 out of 14) of tick species, with the highest prevalence (37.07%) observed in the genus Rhipicephalus. Eight rickettsial species were identified in 2375 livestock samples. Notably, six new Rickettsiales variants/strains were discovered, and Candidatus Rickettsia longicornii was unambiguously identified. Conclusions This large-scale survey provided further insight into the high genetic diversity and overall prevalence of emerging Rickettsiales within endemic hotspots in Yunnan Province. The potential threats posed by these emerging tick-borne Rickettsiales to public health warrant attention, underscoring the need for effective strategies to guide the prevention and control of emerging zoonotic diseases in China. Graphical Abstract

Abstract Angiotensin-converting enzyme (ACE) is closely related to cardiometabolic risk factors and atherosclerosis. This study aims to investigate whether the insertion/deletion (I/D) variant of ACE gene impacts cardiometabolic risk factors, premature coronary artery disease (PCAD), and severity of coronary lesions. PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until December 22, 2023. 94,270 individuals were included for the analysis. Carriers of DD genotype had higher levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), and waist circumference (WC) than carriers of II or ID genotypes. In addition, carriers of DD genotype were at high risk of PCAD and multiple vessel lesions. The impacts of ACE I/D variant on lipid levels were significant in American individuals but stronger in male individuals. In contrast, the impacts of ACE I/D variant on PCAD and severity of coronary lesions were primarily significant in Caucasian individuals. This study indicates that the ACE I/D variant has a slight but significant impact on cardiometabolic risk factors, PCAD, and severity of coronary lesions. Angiotensin-converting enzyme inhibitors (ACEI) may benefit high-risk populations with ACE DD genotype to prevent PCAD and multiple vessel lesions. PROSPERO registration number: CRD42023426732

Abstract Background The latest evidence indicates that ATP-binding cassette superfamily G member 2 (ABCG2) is critical in regulating lipid metabolism and mediating statin or cholesterol efflux. This study investigates whether the function variant loss within ABCG2 (rs2231142) impacts lipid levels and statin efficiency. Methods PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until November 18, 2023. Results Fifteen studies (34,150 individuals) were included in the analysis. The A allele [Glu141Lys amino acid substitution was formed by a transversion from cytosine (C) to adenine (A)] of rs2231142 was linked to lower levels of high-density lipoprotein cholesterol (HDL-C), and higher levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). In addition, the A allele of rs2231142 substantially increased the lipid-lowering efficiency of rosuvastatin in Asian individuals with dyslipidemia. Subgroup analysis indicated that the impacts of rs2231142 on lipid levels and statin response were primarily in Asian individuals. Conclusions The ABCG2 rs2231142 loss of function variant significantly impacts lipid levels and statin efficiency. Preventive use of rosuvastatin may prevent the onset of coronary artery disease (CAD) in Asian individuals with dyslipidemia.

This study investigated the effects of dietary glutamine on growth performance, antioxidant capacity, and osmoregulation in euryhaline fish (Oreochromis niloticus) under hyperosmotic stress. Nile tilapia was fed four diets with varying glutamine concentrations (0 %, 0.75 %, 1.5 %, and 3 %) at 0 or 16 ppt for 42 days. The results demonstrated that dietary supplementation of 0.75 % glutamine significantly enhanced the growth performance of Nile tilapia under both 0 ppt and 16 ppt salinity. Hyperosmotic stress significantly reduced the crude protein and crude lipid contents while elevated the ash content of the fish. Under hyperosmotic stress, dietary glutamine supplementation significantly increased the antioxidant and immune capacities, and attenuated apoptosis in the liver of tilapia. The expression of ion transporter genes in the gills and kidneys were both significantly increased by dietary glutamine. Meanwhile, glutamine supplementation significantly reduced the levels of inorganic ions in serum while increased serum osmolality. Hyperosmotic stress significantly activated the glycolysis, gluconeogenesis, and pentose phosphate pathways in the liver of tilapia. However, supplementation of glutamine under hyperosmotic stress would significantly enhance the ability of gluconeogenesis of tilapia in the liver. The results of this research suggested that dietary glutamine might promote the growth performance of fish by enhancing their antioxidant capacity and osmoregulation capacity under chronic hyperosmotic stress. This work investigates the role of glutamine in osmolarity regulation and extends the understanding of its mechanism of action, which could provide a reference for hyperosmotic adaptation in aquatic animals.

Background: Cardioembolic stroke is a type of ischemic stroke with high disability and mortality, a high recurrence rate and poor prognosis. miRNAs have been explored as potential noninvasive biomarkers in atrial fibrillation and ischemic stroke, but their expression profile in cardioembolic stroke still needs to be explored. This study will explore the differences in miRNA expression between cardioembolic stroke patients and healthy people through meta-analysis and attempt to analyze the target genes by bioinformatics analysis. Methods: Literature databases and gene expression databases were searched from the inception date to June 2022. The study reported the circulating miRNA expression profiles in cardioembolic stroke patients and healthy controls. miRNAs with significantly differential expression and their target genes were analyzed. Results: Three articles and one gene expression dataset were included in the analysis. The results showed that miR-21–5p (SMD: 2.16; 95 % CI: 1.57, 2.75; p

Abstract Hepatic encephalopathy is a neuropsychiatric complication of liver disease which is partly associated with elevated ammonemia. Urea hydrolysis by urease-producing bacteria in the colon is often mentioned as one of the main routes of ammonia production in the body, yet research on treatments targeting bacterial ureases in hepatic encephalopathy is limited. Herein we report a hydroxamate-based urease inhibitor, 2-octynohydroxamic acid, exhibiting improved in vitro potency compared to hydroxamic acids that were previously investigated for hepatic encephalopathy. 2-octynohydroxamic acid shows low cytotoxic and mutagenic potential within a micromolar concentration range as well as reduces ammonemia in rodent models of liver disease. Furthermore, 2-octynohydroxamic acid treatment decreases cerebellar glutamine, a product of ammonia metabolism, in male bile duct ligated rats. A prototype colonic formulation enables reduced systemic exposure to 2-octynohydroxamic acid in male dogs. Overall, this work suggests that urease inhibitors delivered to the colon by means of colonic formulations represent a prospective approach for the treatment of hepatic encephalopathy.

Abstract Background Cytokine storm is known to impact the prognosis of coronavirus disease 2019 (COVID-19), since pro-inflammatory cytokine variants are associated with cytokine storm. It is tempting to speculate that pro-inflammatory cytokines variants may impact COVID-19 outcomes by modulating cytokine storm. Here, we verified this hypothesis via a comprehensive analysis. Methods PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until December 15, 2023. Case–control or cohort studies that investigated the impacts of rs1800795 or rs1800629 on COVID-19 susceptibility, severity, mortality, IL-6, TNF-α, or CRP levels were included after an anonymous review by two independent reviewers and consultations of disagreement by a third independent reviewer. Results 47 studies (8305 COVID-19 individuals and 17,846 non-COVID-19 individuals) were analyzed. The rs1800629 A allele (adenine at the −308 position of the promoter was encoded by the A allele) was associated with higher levels of tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). In contrast, the rs1800795 C allele (cytosine at the −174 position of the promoter was encoded by the C allele) was linked to higher levels of interleukin-6 (IL-6) and CRP. In addition, the A allele of rs1800629 increased the severity and mortality of COVID-19. However, the C allele of rs1800795 only increased COVID-19 susceptibility. Conclusions rs1800629 and rs1800795 variants of pro-inflammatory cytokines have significant impacts on systemic inflammatory profile and COVID-19 clinical outcomes. rs1800629 may serve as a genetic marker for severe COVID-19.

Abstract 1-(4-ethylphenyl)-nonane-1,3-dione (0206) is an oil-soluble liquid molecule with rod-like structure. In this study, the chelate (0206-Fe) with octahedral structure was prepared by the reaction of ferric chloride and 1,3-diketone. The experimental results show that when using 0206 and a mixed solution containing 60% 0206-Fe and 40% 0206 (0206-Fe(60%)) as lubricants of the steel friction pairs, superlubricity can be achieved (0.007, 0.006). But their wear scar diameters (WSD) were very large (532 µm, 370 µm), which resulted in the pressure of only 44.3 and 61.8 MPa in the contact areas of the friction pairs. When 0206-Fe(60%) was mixed with PAO6, it was found that the friction coefficient (COF) decreased with increase of 0206-Fe(60%) in the solution. When the ratio of 0206-Fe(60%) to PAO6 was 8:2 (PAO6(20%)), it exhibited better comprehensive tribological properties (232.3 MPa). Subsequent studies have shown that reducing the viscosity of the base oil in the mixed solution helped to reduce COF and increased WSD. Considering the COF, contact pressure, and running-in time, it was found that the mixed lubricant (Oil3(20%)) prepared by the base oil with a viscosity of 19.7 mPa·s (Oil3) and 0206-Fe(60%) exhibited the best tribological properties (0.007, 161.4 MPa, 3,100 s).

The experiment was conducted to investigate the influence of dietary CuO nanoparticles (CuO NPs) on growth performance, muscle development, antioxidant capacity, and inflammatory responses of juvenile yellow catfish Pelteobagrus fulvidraco. The three diets were formulated with CuO NPs addition at 0 (without CuO NPs addition, low-Cu group, control), 9 (middle-Cu group), and 15 (high-Cu group) mg kg−1 diet, respectively, and final dietary levels for three diets were 2.07 (low-Cu group: served as a control group), 9.19 (middle-Cu group), and 13.96 mg kg−1 (high-Cu group), respectively. Each diet was randomly assigned to three replicate groups of 60 fish. The feeding experiment continued for 12 weeks. Among three dietary groups, yellow catfish juveniles fed a middle Cu diet possessed the highest growth performance, and the lowest feed utilization (P0.05). The Cu content in muscle tissue increased with increasing dietary Cu levels. CuO NPs fortification in the diets influenced mRNA of genes involved in endocytosis and metal ion transpor (P

Background: Borrelia miyamotoi is a spirochete species transmitted via hard ticks. Following its discovery in Japan, this pathogen has been detected around the world, and is increasingly confirmed as a human pathogen causing febrile disease, namely relapsing fever. Its presence has been confirmed in the Northeast China. However, there is little information regarding the presence of B. miyamotoi and other hard-tick-borne relapsing fever spirochetes in southern China including Yunnan province, where tick and animal species are abundant and many people both inhabit and visit for recreation. Methods: For the present study, we collected samples of ticks, wildlife, and domestic animal hosts from different counties in Yunnan province. Nucleic acids from samples were extracted, and the presence of B. miyamotoi and other relapsing fever spirochetes was confirmed using polymerase chain reaction (PCR) for the 16S rRNA specific target gene fragment. The positive samples were then amplified for partial genome of the flaB and glpQ genes. Statistical differences in its distribution were analyzed by SPSS 20 software. Sequence of partial 16S rRNA, flaB and glpQ genome were analyzed and phylogenetic trees were constructed. Results: A total of 8260 samples including 2304 ticks, 4120 small mammals and 1836 blood of domestic animal hosts were collected for screening for infection of B. miyamotoi and other relapsing fever spirochetes. Cattle and sheep act as the main hosts and Rhipicephalus microplus, Haemaphysalis nepalensis, H. kolonini and Ixodes ovatus were identified as the important vector host with high prevalence or wide distribution. Only one Mus caroli (mouse) and one Sorex alpinus (shrew) were confirmed positive for relapsing fever spirochetes. Evidence of vertical transmission in ticks was also confirmed. Two known strains of B. miyamotoi and one novel relapsing fever spirochetes, B. theileri-like agent, were confirmed and described with their host adaptation, mutation, and potential risk of spreading and spillover for human beings. Conclusions: Our results provide new evidence of relapsing fever spirochetes in vector and animal hosts in Yunnan province based on large sample sizes, and offer guidance on further investigation, surveillance and monitoring of this pathogen.

Abstract Conventional venipuncture is invasive and challenging in low and middle‐income countries. Conversely, point‐of‐care devices paired with fingersticks, although less invasive, suffer from high variability and low blood volume collection. Recently approved microsampling devices address some of these issues but remain cost‐prohibitive for resource‐limited settings. In this work, a cost‐effective microsampling device is described for the collection of liquid blood with minimal invasiveness and sufficient volume retrieval for laboratory analyses or immediate point‐of‐care testing. Inspired by the anatomy of sanguivorous leeches, the single‐use device features a storage compartment for blood collection and a microneedle patch hidden within a suction cup. Finite Element Method simulations, corroborated by mechanical analyses, guide the material selection for device fabrication and design optimization. In piglets, the device successfully collects ≈195 µL of blood with minimal invasiveness. Additionally, a tailor‐made lid and adapter enable safe fluid transportation and integration with commercially available point‐of‐care systems for on‐site analyses, respectively. Taken together, the proposed platform holds significant promise for enhancing healthcare in the pediatric population by improving patient compliance and reducing the risk of needlestick injuries through concealed microneedles. Most importantly, given its cost‐effective fabrication, the open‐source microsampling device may have a meaningful impact in resource‐limited healthcare settings.

In order to explore the effect of nitrogen deposition on physiological response of mosses in Jiuzhaigou, Sichuan Province, the local dominant mosses Actinothuidium hookeri and Hylocomium splendens were taken as the research objects, and NH4NO3 was used as the nitrogen source. Nitrogen deposition treatments were applied with control (0 kg N·hm-2·a-1), low (20 kg N·hm-2·a-1) and high (50 kg N·hm-2·a-1). The experiment lasted six months. The results were as follows: (1) The contents of reactive oxygen species, malondialdehyde, chlorophyll, proline and soluble protein were significantly increased by application of NH4NO3 solution. At the same time, the activities of its catalase, peroxidase, superoxide dismutase and ascorbate peroxidase were significantly increased when Actinothuidium hookeri was subjected to nitrogen deposition. (2) During the vigorous and late periods, the activities of its catalase, peroxidase and ascorbate peroxidase were significantly decreased when Hylocomium splendens was subjected to similar nitrogen deposition. (3) During the experiment, subordinate function value of Actinothuidium hookeri significantly increased with increase of NH4NO3 solution concentration. Response pattern of subordinate function value was different when Hylocomium splendens was subjected to different concentrations of NH4NO3 solution in the vigorous and late growth periods. In conclusion, physiological responses are different between two mosses subjected to nitrogen deposition. High concentration of nitrogen deposition can promote the growth of Actinothuidium hookeri. Hylocomium splendens can grow normally under the natural nitrogen deposition conditions and can withstand a certain degree of nitrogen deposition, but when the nitrogen deposition is too high, it will cause damage to it, the metabolism decreases and its growth is inhibited. Long-term nitrogen deposition may lead to future change of moss community composition in Jiuzhaigou, Sichuan Province.

Abstract Objective The purpose of this study was to investigate the combined effect of self-reported sleep durations and physical activity (PA) on all cause and cardiovascular diseases mortality. Methods Twenty-nine thousand fifty-eight participants (48.5% male, median age 49 years) from the National Health and Nutrition Examination Survey cycles 2007 to 2016 were included. We classified sleep duration into five categories (

Abstract Developing multiplex PCR assays requires extensive experimental testing, the number of which exponentially increases by the number of multiplexed targets. Dedicated efforts must be devoted to the design of optimal multiplex assays ensuring specific and sensitive identification of multiple analytes in a single well reaction. Inspired by data-driven approaches, we reinvent the process of developing and designing multiplex assays using a hybrid, simple workflow, named Smart-Plexer, which couples empirical testing of singleplex assays and computer simulation to develop optimised multiplex combinations. The Smart-Plexer analyses kinetic inter-target distances between amplification curves to generate optimal multiplex PCR primer sets for accurate multi-pathogen identification. In this study, the Smart-Plexer method is applied and evaluated for seven respiratory infection target detection using an optimised multiplexed PCR assay. Single-channel multiplex assays, together with the recently published data-driven methodology, Amplification Curve Analysis (ACA), were demonstrated to be capable of classifying the presence of desired targets in a single test for seven common respiratory infection pathogens.

Abstract Background Plant organs grow in a certain direction and organ twisted growth, a rare and distinctive trait, is associated with internal structure changes and special genes. The twisted branch mutant of Chinese jujube jujube, an important fruit tree native to China and introduced to nearly 50 countries, provides new typical materials for exploration of plant twisted growth. Results In this study, the cytological characteristics and related genes of twisted branches in Chinese jujube were revealed by microscopy observation and transcriptome analysis. The unique coexistence of primary and secondary structures appeared in the twisted parts of branches, and special structures such as collateral bundle, cortical bundles, and internal phloem were formed. Ninety differentially expressed genes of ‘Dongzao’ and its twisted mutant were observed, in which ZjTBL43, ZjFLA11, ZjFLA12 and ZjIQD1 were selected as candidate genes. ZjTBL43 was homologous to AtTBL43 in Arabidopsis, which was involved in the synthesis and deposition of cellular secondary wall cellulose. The attbl43 mutant showed significant inflorescence stem bending growth. The transgenic lines of attbl43 with overexpression of ZjTBL43 were phenotypically normal.The branch twisted growth may be caused by mutations in ZjTBL43 in Chinese jujube. AtIQD10, AtFLA11 and AtFLA12 were homologous to ZjIQD1, ZjFLA11 and ZjFLA12, respectively. However, the phenotype of their function defect mutants was normal. Conclusion In summary, these findings will provide new insights into the plant organ twisted growth and a reference for investigation of controlling mechanisms of plant growth direction.

Abstract Digital light processing (DLP) of structurally complex poly(ethylene glycol) (PEG) hydrogels with high mechanical toughness represents a long‐standing challenge in the field of 3D printing. Here, we report a 3D printing approach for the high‐resolution manufacturing of structurally complex and mechanically strong PEG hydrogels via heat‐assisted DLP. Instead of using aqueous solutions of photo‐crosslinkable monomers, PEG macromonomer melts were first printed in the absence of water, resulting in bulk PEG networks. Then, post‐printing swelling of the printed networks was achieved in water, producing high‐fidelity 3D hydrogels with complex structures. By employing a dual‐macromonomer resin containing a PEG‐based four‐arm macrophotoinitiator, “all‐PEG” hydrogel constructs were produced with compressive toughness up to 1.3 MJ m−3. By this approach, porous 3D hydrogel scaffolds with trabecular‐like architecture were fabricated, and the scaffold surface supported cell attachment and the formation of a monolayer mimicking bone‐lining cells. This study highlights the promises of heat‐assisted DLP of PEG photopolymers for hydrogel fabrication, which may accelerate the development of 3D tissue‐like constructs for regenerative medicine.

The present study was performed to investigate yellow catfish manganese (Mn) requirement with Mn dioxide nanoparticles (MnO2NPs) as Mn source, and to evaluate effects of dietary Mn on growth performance, Mn metabolism and kidney health. Using MnO2NPs as the Mn sources, six experimental diets were formulated with dietary Mn levels at 1.67, 4.35, 7.37, 13.63, 26.06 and 50.37 mg Mn/kg diet, respectively, and fed to yellow catfish for 8 weeks. Yellow catfish growth performance and feed intake were the highest in the group of 13.63 mg Mn/kg diet, and the lowest in the group of 1.67 mg Mn/kg diet; and the feed conversion rate showed opposite trend with growth performance. Dietary Mn addition increased Mn content in the whole body, kidney and serum. The mRNA abundances of dmt1, zip8 and znt10 increased with the increase of dietary Mn level. Yellow catfish fed high dietary MnO2NPs level had higher mRNA abundances of dynamin1, dynamin2, cav1, cltc and eps15. Dietary Mn excess damaged the kidney histology. Yellow catfish fed the 13.63 mg Mn/kg diet had higher T-AOC, T-SOD, Mn-SOD, CAT activities, and mRNA levels of sod1, sod2 and cat (antioxidant response), but lower mRNA abundances of grp78, ire1, perk and atf4 (endoplasmic reticulum stress), tnfα, il1β and il6 (inflammatory response). The broken-line analysis of WG and the linear regression of whole-body Mn retention against dietary Mn levels showed that optimal Mn requirement was 12.57 mg Mn/kg diet and 8.33 mg Mn/kg diet, respectively, with MnO2NPs as Mn source. For the first time, we explored the effects of dietary MnO2 nanoparticles on growth performance, Mn uptake and metabolism, antioxidant responses, endoplasmic reticulum stress and inflammatory responses of the kidney, and determined the optimal dietary Mn requirement of yellow catfish fed MnO2 nanoparticles-added diet.

This study exposed high-oleic rapeseed oil (HORO) to different pretreatment (microwave or roasting) and processing methods to investigate (cold pressing, hexane extraction, subcritical butane extraction, and aqueous enzymatic extraction) the effects of processing technologies on HORO parameters associated with its physicochemical properties, endogenous antioxidant substances, and antioxidant capacity. The oil yield of various processing technologies was between 35.4% and 59.7%, and the fatty acid composition did not significantly differ. Hierarchical clustering and principal component analyses were used for evaluation. The results revealed that the microwave pretreatment–hexane extraction (M-HE) method resulted in significantly higher levels of tocopherols (688.4 mg/kg), polyphenols (1007.76 mg/kg), and phytosterols (1810.6 mg/kg) in HORO, implying strong free radical scavenging capacity (DPPH-oil: 79.63, DPPH-nonpolar: 71.42, DPPH-polar: 6.65, FRAP: 55.4, ABTS: 3043.7 μmol TE/kg). Hence, M-HE is a promising method for producing HORO with a higher stability and nutritional value.

Abstract Background Ribonuclease (RNase T2) plays crucial roles in plant evolution and breeding. However, there have been few studies on the RNase T2 gene family in Ziziphus jujuba Mill., one of important dried fruit tree species. Recently, the released sequences of the reference genome of jujube provide a good chance to perform genome-wide identification and characterization of ZjRNase gene family in the jujube. Results In this study, we identified four members of RNase T2 in jujube distributed on three chromosomes and unassembled chromosomes. They all contained two conserved sites (CASI and CASII). Analysis of the phylogenetic relationships revealed that the RNase T2 genes in jujube could be divided into two groups: ZjRNase1 and ZjRNase2 belonged to class I, while ZjRNase3 and ZjRNase4 belonged to class II. Only ZjRNase1 and ZjRNase2 expression were shown by the jujube fruit transcriptome analysis. So ZjRNase1 and ZjRNase2 were selected functional verification by overexpression transformation of Arabidopsis. The overexpression of these two genes led to an approximately 50% reduction in seed number, which deserve further attention. Moreover, the leaves of the ZjRNase1 overexpression transgenic lines were curled and twisted. Overexpression of ZjRNase2 resulted in shortened and crisp siliques and the production of trichomes, and no seeds were produced. Conclusion In summary, these findings will provide new insights into the molecular mechanisms of low number of hybrid seeds in jujube and a reference for the future molecular breeding of jujube.

Abstract Background Phosphorus commonly reduces lipid deposition in the vertebrates. However, the underlying mechanisms involved in the process remain unclear. Methods Yellow catfish were given three experimental diets with dietary phosphate levels of 3.22, 6.47 and 7.99 g Pi kg− 1, respectively, for 8 weeks. The contents of triglyceride, non-esterified free fatty acids, adenosine triphosphate, nicotinamide adenine dinucleotide, nicotinamide adenine dinucleotide, enzymatic activities, mRNA and protein expression were determined in the intestinal tissues. Hematoxylin and eosin, Oil Red O staining, and transmission electron microscope were performed for intestinal tissues. Primary intestinal epithelial cells were isolated from yellow catfish intestine. Western blot analysis, Immunoprecipitation assays, Immunofluorescence staining, and RNA extraction and quantitative real-time PCR were decided. Luciferase reporter assays and electrophoretic mobility shift assay were used to evaluate the function of Sirt3, PPARα and Lcad promoters. Results High dietary phosphate intake activated intestinal phosphate absorption and excretion, and reduced lipid deposition through increasing lipolysis in the intestine. Moreover, phosphate incubation increased the mRNA and protein expression of krüppel like factor 4 (klf4), silent mating-type information regulation 2 homolog 3 (sirt3), peroxisome proliferator activated receptor alpha (pparα) and long chain acyl-CoA dehydrogenase (lcad) in the intestinal epithelial cells (IECs), and klf4 knockdown attenuated the phosphate-induced increase of protein levels of Sirt3, Pparα and Lcad. Further investigation found that Klf4 overexpression increased the activity of sirt3 and pparα promoters, which in turn reduced the acetylation and protein level of Lcad. Conclusion Dietary Pi excess induced lipid degradation by the activation of the Klf4-Sirt3/Pparα-Lcad pathway in the intestine and primary IECs. Graphical Abstract Video Abstract

Cadmium (Cd) is a carcinogenic environmental pollutant that harms male reproductive systems by lowering sperm quality, impairing spermatogenesis, and causing apoptosis. Although zinc (Zn) has been reported to alleviate Cd toxicity, the underlying mechanisms have not been fully elucidated. The aim of this work was to investigate the mitigating effects of Zn on Cd-induced male reproductive toxicity in the freshwater crab Sinopotamon henanense. Cd exposure not only resulted in its accumulation but also in Zn deficiency, decreased sperm survival rate, poor sperm quality, altered ultrastructure, and increased apoptosis in the testis of the crabs. Morever, Cd exposure increased the expression and distribution of metallothionein (MT) in the testis. However, Zn supplementation effectively mitigated the aforementioned effects of Cd, as demonstrated by preventing Cd accumulation, increasing Zn bioavailability, alleviating apoptosis, increasing mitochondrial membrane potential, decreasing reactive oxygen species (ROS) levels, and restoring MT distribution. Moreover, Zn also significantly reduced the expression of apoptosis-related (p53, Bax, CytC, Apaf-1, Caspase-9, Caspase-3), metal transporter-related ZnT1, metal-responsive transcription factor 1 (MTF1), and the gene and protein expression of MT, while increasing the expression of ZIP1 and Bcl-2 in the testis of Cd-treated crabs. In conclusion, Zn alleviates Cd-induced reproductive toxicity via regulating ion homeostasis, MT expression, and inhibiting mitochondria-mediated apoptosis in the testis of S. henanense. The information obtained in this study may serve as the foundation for further investigation into the development of mitigation strategies for adverse ecological and human health outcomes associated with Cd contamination or poisoning.

The current research was aimed to determine the impacts of cottonseed meal substitution levels for fishmeal on the growth performance, immune indices, antioxidant ability, and muscle texture of red swamp crayfish (Procambarus clarkii). Five isonitrogenous and isolipidic diets were formulated to feed the crayfish for 8 weeks. The basal diet contained 20% fishmeal (FM), while the other four experimental diets substituted fishmeal in FM diet with cottonseed meal at levels of 25%, 50%, 75%, and 100%, referred to as CM25, CM50, CM75, and CM100 respectively. A total of 750 crayfish with an average initial weight of 4.00 g were selected and randomly allocated to fifteen cages. Each diet was randomly assigned to triplicate groups of crayfish. Weight gain and specific growth rate declined, and feed conversion rate, asparate aminotransferase and alanine transaminase activities appear to increase as cottonseed meal substitution levels increased. Serum total cholesterol levels declined in crayfish fed CM100 diet compared to crayfish fed the FM diet. Serum phenoloxidase and lysozyme activities, and muscle hardness and mef-2a mRNA expression were the highest for crayfish fed fishmeal-based diet and showed no significant difference among other four groups. Dietary cottonseed meal levels did not significantly influence hepatopancreas index, viscerosomatic index, condition factor, serum glucose, triglyceride, albumin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and creatinine contents, as well as the contents of acid phosphatase, and alkaline phosphatase, and muscle texture profile (cohesiveness, springiness, adhesiveness, and chewiness) and mef-2b and mstn mRNA expression. High dietary fish meal replacement by cottonseed meal tended to upregulate mRNA expression of nuclear factor erythroid 2-related factor 2, glutathione peroxidase, glutathione reductase, manganese superoxide dismutase, glutathione S-transferase, and catalase. Taken together, dietary cottonseed meal reduced growth performance and feed utilization, induced hepatopancreas oxidative stress, and influenced some serum and muscle parameters. The gossypol content and unbalanced amino acid profile are considered the limiting factor influencing the fish meal replacement by cottonseed meal.

Three diets were formulated with dietary zinc (Zn) levels at 12.10 mg Zn/kg (L-Zn), 18.69 mg Zn/kg (M-Zn) and 120.82 mg Zn/kg (H-Zn) to explore effects of dietary Zn on growth, nutrient composition, muscle development, antioxidant and inflammatory responses in the muscle tissues of yellow catfish, one of the important economic fish in several Asian countries, including China. Zn content in M-Zn group could meet Zn requirement of yellow catfish. 270 juvenile yellow catfish (4.97 ± 0.01 g, mean ± S.E.M) were stocked in nine 300-L indoors tanks, 30 yellow catfish in each tank, and randomly provided with three diets for 10 weeks. Among three treatments, yellow catfish fed the middle Zn diets showed higher growth performance and condition factor but lower feed conversion rate than those fed the high Zn diets. Dietary Zn addition increased muscle Zn contents, but did not significantly influence feed intake, viscerosomatic and hepatosomatic index, survival, moisture, lipid, crude protein and ash contents in the muscle. Dietary Zn levels significantly influenced mRNA expression of several muscle development-related genes, such as mef2a, myod, myf5, myog, mef2d, pax7, mrf4, myhc and mstn. Middle dietary Zn levels increased antioxidant capability and reduced oxidative stress, as evaluated by enzymatic activities, gene and protein expression related to antioxidant response. Fish fed the middle Zn diets had the lower il8, tnf-α and tnf-β mRNA expression but higher il10 and tgf-β mRNA expression than those fed the high Zn diet, suggesting that optimal dietary Zn levels activated anti-inflammatory response and inhibited pro-inflammatory responses. Based on the observation, our study suggested that the suitable dietary Zn levels promoted the growth, muscle development, antioxidant and anti-inflammatory responses in fish.

Background Thalassaemia is one of the most common inherited monogenic diseases worldwide with a heavy global health burden. Considering its high prevalence in low and middle-income countries, a cheap, accurate and high-throughput screening test of thalassaemia prior to a more expensive confirmatory diagnostic test is urgently needed. Methods In this study, we constructed a machine learning model based on MALDI-TOF mass spectrometry quantification of haemoglobin chains in blood, and for the first time, evaluated its diagnostic efficacy in 674 thalassaemia (including both asymptomatic carriers and symptomatic patients) and control samples collected in three hospitals. Parameters related to haemoglobin imbalance (α-globin, β-globin, γ-globin, α/β and α-β) were used for feature selection before classification model construction with 8 machine learning methods in cohort 1 and further model efficiency validation in cohort 2. Results The logistic regression model with 5 haemoglobin peak features achieved good classification performance in validation cohort 2 (AUC 0.99, 95% CI 0.98–1, sensitivity 98.7%, specificity 95.5%). Furthermore, the logistic regression model with 6 haemoglobin peak features was also constructed to specifically identify β-thalassaemia (AUC 0.94, 95% CI 0.91–0.97, sensitivity 96.5%, specificity 87.8% in validation cohort 2). Conclusions For the first time, we constructed an inexpensive, accurate and high-throughput classification model based on MALDI-TOF mass spectrometry quantification of haemoglobin chains and demonstrated its great potential in rapid screening of thalassaemia in large populations.Key messages Thalassaemia is one of the most common inherited monogenic diseases worldwide with a heavy global health burden. We constructed a machine learning model based on MALDI-TOF mass spectrometry quantification of haemoglobin chains to screen for thalassaemia.

The Ziziphus mauritiana Lam. and Z. jujuba Mill. are the two most economically important members of the genus Ziziphus. The fruit color of Z. mauritiana remains green throughout fruit development in the majority of commercial cultivars, whereas its close relative, Z. jujuba Mill. turns from green to red in all cultivars. However, the lack of transcriptomic and genomic information confines our understanding of the molecular mechanisms underlying fruit coloration in Z. mauritiana (Ber). In the present study, we performed the transcriptome-wide analysis of MYB transcription factors (TFs) genes in Z. mauritiana and Z. jujuba, and identified 56 ZmMYB and 60 ZjMYB TFs in Z. mauritiana and Z. jujuba, respectively. Through transcriptomic expression analysis, four similar MYB genes (ZmMYB/ZjMYB13, ZmMYB/ZjMYB44, ZmMYB/ZjMYB50, and ZmMYB/ZjMYB56) from Z. mauritiana and Z. jujuba were selected as candidate key genes regulating flavonoid biosynthesis. Among these genes, the ZjMYB44 gene was transiently highly expressed in fruit, and flavonoid content accumulation also increased, indicating that this gene can influence flavonoid content during the period of fruit coloration in Z. jujuba. The current study adds to our understanding of the classification of genes, motif structure, and predicted functions of the MYB TFs, as well as identifying MYBs that regulate flavonoid biosynthesis in Ziziphus (Z. mauritiana and Z. jujuba). Based on this information, we concluded that MYB44 is involved in the flavonoids biosynthesis pathway during the fruit coloring of Ziziphus. Our research results provide an important understanding of the molecular mechanism of flavonoid biosynthesis resulting in fruit coloration and laying a foundation for further genetic improvement of fruit color in Ziziphus.

Background. Emerging evidence indicates tribbles homolog 1 (Trib1) protein may be involved in lipid metabolism regulation and coronary artery disease (CAD) pathogenesis. However, whether TRIB1 gene variants affect lipid levels and CAD remains elusive, this study is aimed at clarifying the effect of TRIB1 variants on lipid profile and CAD. Methods. By searching PubMed and Cochrane databases for studies published before December 18, 2022, a total of 108,831 individuals were included for the analysis. Results. The outcomes of the analysis on all individuals showed that the A allele carriers of rs17321515 and rs2954029 variants had higher low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels than the noncarriers. Consistently, a higher CAD risk was observed in the A allele carriers. Subgroup analysis indicated that increased LDL-C, TC, and CAD risk were observed in Asian population. Conclusions. Variants of TRIB1 (i.e., rs17321515 and rs2954029) may serve as causal genetic markers for dyslipidemia and CAD in Asian population.

The novel sugar transporter known as SWEET (sugars will eventually be exported transporter) is involved in the transport and distribution of photosynthesis products in plants. The SWEET protein is also involved in pollen development, nectar secretion, stress responses, and other important physiological processes. Although SWEET genes have been characterized and identified in model plants, such as Arabidopsis and rice, little is known about them in jujube. In this study, the molecular characteristics of the SWEET gene family in the Chinese jujube (Ziziphus jujuba Mill.) and their expression patterns in different organs, at different fruit developmental stages, and under abiotic stress were analyzed. A total of 19 ZjSWEET genes were identified in jujube through a genome-wide study; these were classified into four sub-groups based on their phylogenic relationships. The gene structure analysis of ZjSWEET genes showed that all the members had introns. The expression patterns of different ZjSWEET genes varied significantly in different organs (root, shoot, leave, flower, fruit), which indicated that ZjSWEETs play different roles in multiple organs. According to the expression profiles by quantitative real-time PCR analysis during fruit development, the expression levels of the two genes (ZjSWEET11, ZjSWEET18) gradually increased with the development of the fruit and reached a high level at the full-red fruit stage. A prediction of the cis-acting regulatory elements indicated that the promoter sequences of ZjSWEETs contained nine types of phytohormone-responsive cis-regulatory elements and six environmental factors. In addition, the expression profiles by quantitative real-time PCR analysis showed that some of the ZjSWEETs responded to environmental changes; ZjSWEET2 was highly induced in response to cold stress, and ZjSWEET8 was significantly up-regulated in response to alkali and salt stresses. This study showed that the functions of the ZjSWEET family members of jujube are different, and some may play an important role in sugar accumulation and abiotic stress in jujube.

This research was conducted to investigate the effects of four dietary zinc (Zn) sources on growth performance, Zn metabolism, antioxidant capacity, endoplasmic reticulum (ER) stress, and tight junctions in the intestine of grass carp Ctenopharyngodon idella. Four Zn sources consisted of Zn dioxide nanoparticles (ZnO NPs), Zn sulfate heptahydrate (ZnSO4·7H2O), Zn lactate (Zn-Lac), and Zn glycine chelate (Zn-Gly), respectively. Grass carp with an initial body weight of 3.54 g/fish were fed one of four experimental diets for 8 weeks. Compared to inorganic Zn (ZnSO4·7H2O), grass carp fed the ZnO NPs and Zn-Gly diets exhibited better growth performance. Furthermore, grass carp fed the organic Zn (Zn-Lac and Zn-Gly) diets displayed enhanced Zn transport activity, improved intestinal histology, and increased intestinal tight junction-related genes expression compared to other groups. In comparison to other Zn sources, dietary ZnO NPs caused increased Zn deposition and damaged antioxidation capacity by suppressing antioxidant enzymatic activities and related gene expression in the intestine. Grass cap fed the ZnO NPs diet also exhibited lower mRNA abundance of endoplasmic reticulum (ER) stress- and tight junction-associated genes. According to the above findings, it can be concluded that dietary organic Zn addition (Zn-Lac and Zn-Gly) is more beneficial for intestinal health in grass carp compared to inorganic and nanoform Zn sources. These findings provide valuable insights into the application of organic Zn sources, specifically Zn-Lac and Zn-Gly, in the diets for grass carp and potentially for other fish species.

Daqu can be divided into artificially pressed daqu (A-Daqu) and mechanically pressed daqu (M-Daqu) based on pressing patterns. Here, we compared the discrepancies in physicochemical properties, volatile metabolites, and microbiota features between A-Daqu and M-Daqu during fermentation and further investigated the factors causing those differences. A-Daqu microbiota was characterized by six genera (e.g., Bacillus and Thermoactinomyces), while five genera (e.g., Bacillus and Thermomyces) dominated in M-Daqu. The flavor compounds analysis revealed that no obvious difference was observed in the type of esters between the two types of daqu, and M-Daqu was enriched with more alcohols. The factors related to differences between the two types of daqu were five genera (e.g., Hyphopichia). The functional prediction of microbial communities revealed that the functional discrepancies between the two types of daqu were mainly related to ethanol metabolism and 2,3-butanediol metabolism. This study provided a theoretical basis for understanding the heterogeneity of daqu due to the different pressing patterns.

BackgroundSeveral 9p21.3 variants, such as rs1333049, rs4977574, rs10757274, rs10757278, and rs10811661, identified from recent genome-wide association studies (GWASs) are reported to be associated with coronary artery disease (CAD) susceptibility but independent of dyslipidemia. This study investigated whether these 9p21.3 variants influenced lipid profiles.Methods and resultsBy searching the PubMed and Cochrane databases, 101,099 individuals were included in the analysis. The consistent finding for the rs1333049 C allele on lipid profiles increased the triglyceride (TG) levels. Moreover, the rs4977574 G allele and the rs10757274 G allele, respectively, increased low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels. However, the rs10811661 C allele largely reduced LDL-C levels. Subgroup analyses indicated that the effects of the rs1333049 C allele, rs4977574 G allele, and rs10757274 G allele on lipid profiles were stronger in Whites compared with Asians. In contrast, the effect of the rs10811661 C allele on lipid profiles was stronger in Asians compared with Whites.ConclusionThe rs1333049 C allele, rs4977574 G allele, and rs10757274 G allele of lncRNA, and the rs10811661 G allele of CDKN2A/2B had a significant influence on lipid levels, which may help the understanding of the underlying mechanisms between 9p21.3 variants and CAD.

Mitochondrial RNA editing plays crucial roles in the plant development and environmental adaptation. Pentatricopeptide repeat (PPR) genes, which are involved in the regulating mitochondrial RNA editing, are potential gene resources in the improvement of rice drought tolerance. In this study, we investigated genome-wide mitochondrial RNA editing in response to drought between upland and lowland rice. Responses of mitochondrial RNA editing to drought exhibit site-specific and genotype-specific patterns. We detected 22 and 57 ecotype-differentiated editing sites under well-watered and drought-treated conditions, respectively. Interestingly, the RNA editing efficiency was positively correlated with many agronomic traits, while it was negatively correlated with drought tolerance. We further selected two mitochondrial-localized PPR proteins, PPR035 and PPR406, to validate their functions in drought tolerance. PPR035 regulated RNA editing at rps4-926 and orfX-406, while PPR406 regulated RNA editing at orfX-355. The defectiveness in RNA editing at these sites had no apparent penalties in rice respiration and vegetative growth. Meanwhile, the knockout mutants of ppr035 and ppr406 show enhanced drought- and salt tolerance. PPR035 and PPR406 were under the balancing selection in upland rice and highly differentiated between upland and lowland rice ecotypes. The upland-dominant haplotypes of PPR035 and PPR406 shall contribute to the better drought tolerance in upland rice. They have great prospective in the improvement of rice drought tolerance.

Amino acids are an essential group of compounds involved in protein synthesis and various metabolic and immune reactions in the human body. Chinese jujubes (Ziziphus jujuba Mill.) are an important fruit and medicinal plant which are native to China and have been introduced into around 50 countries. However, systematic research on the composition and content diversity of amino acids in the jujube is still lacking. In this experiment, the amino acid composition and the contents of the dominant amino acids in the fruit of 161 cultivars of jujube were determined by HPLC. Of the twenty-one kinds of amino acids detected, a total of fourteen kinds of amino acids were detected, of which eight kinds of amino acids were relatively high, including five essential amino acids (threonine, valine, isoleucine, leucine, and phenylalanine) and three nonessential amino acids (glycine, alanine, and proline). However, the contents of the remaining six amino acids were relatively low (aspartic acid, glutamic acid, histidine, serine, arginine, and tryptophan). Therefore, the eight primary amino acids were used as the index to evaluate the amino acids of 161 jujube varieties. Proline accounts for 56.8% of the total amino acid content among the eight amino acids. The total content of the eight primary amino acids in most jujube varieties was 1–1.5 g/100 g, and the highest content of ‘Zaoqiangmalianzao’ was 2.356 g/100 g. The average content of proline was 6.01–14.84 times that of the other seven amino acids. According to the WHO/FAO revised model spectrum of ideal essential amino acids for humans, 19 cultivars met the E/T (essential amino acids/total amino acids) standard, and their values ranged from 35% to 45%; 12 cultivars meet E/NE (non-essential amino acids) ≥ 60%. All cultivars reached the requirement of BC (branched–chain amino acids)/E ≥ 40% with 15 cultivars over 68%. One hundred and fifty-seven cultivars reach the standard of BC/A (aromatic amino acids) ≈ 3.0~3.5. The amino acid ratio coefficient analysis showed that phenylalanine was the first limiting amino acid of all the jujube cultivars. The SRC (the score of amino acid ratio coefficient) values of 134 cultivars were between 50% and 70%, with 12 cultivars over 70%, indicating that jujube fruits are of high nutritional value in terms of amino acids. Based on the principal component analysis and comprehensive ranking of amino acid nutritional value, the top five cultivars were screened from the 161 ones tested, i.e., ‘Tengzhouchanghongzao’, ‘Xinzhengxiaoyuanzao’, ‘Hanguowudeng’, ‘Xuputiansuanzao’, and ‘Lichengxiaozao’. This study established, firstly, a complete basic data analysis of amino acid content in jujube fruit which could be used to select germplasm resources suitable for developing functional amino acid food, and provide theoretical support for the high value utilization of amino acids in jujubes.

BackgroundRecent studies have shown that the 4G/5G insertion/deletion variant of SERPINE1 (rs1799889) is closely linked to coronary artery disease (CAD). This study aims to clarify the effects of the rs1799889 variant on lipid levels and to insight into the mechanisms underlying the rs1799889 variant and CAD.Methods and ResultsBy searching PubMed and the Cochrane databases for studies published before 31 October 2021, 40 studies conducted on a total of 13,117 subjects were included for the analysis. The consistent findings for the effects of the 5G allele of rs1799889 variant on lipid metabolism were the significantly decreased triglycerides (TG) [standardized mean difference (SMD) = –0.12, 95% CI = –0.21 to 0.03, P = 0.01], total cholesterol (TC) (SMD = –0.12, 95% CI = –0.17 to 0.06, P < 0.001), and low-density lipoprotein cholesterol (LDL-C) (SMD = –0.13, 95% CI = –0.23 to 0.03, P = 0.01) levels. Intriguingly, the significant effects of the rs1799889 variant on LDL-C (SMD = –0.15, 95% CI = –0.26 to 0.05, P < 0.01) and TC (SMD = –0.17, 95% CI = –0.27 to 0.07, P < 0.01) levels were primarily observed in the Asian population. However, the significant effect of the rs1799889 variant on high-density lipoprotein cholesterol (HDL-C) (SMD = 0.26, 95% CI = 0.03–0.48, P = 0.03) levels was detected only in female subjects.ConclusionThe rs1799889 variant of SERPINE1 is a protective genetic factor against CAD, the Asian population with the 5G allele of the rs1799889 variant may have a reduced CAD risk.

Chinese jujube (Ziziphus jujuba Mill.) and its wild ancestor, sour jujube (Z. acidojujuba C.Y. Cheng & M.J. Liu), is a Ziziphus genus in the Rhamnaceae family. ZJ and ZA are rich in a variety of active ingredients, with triterpenoids being a unique active ingredient, which are present in the fruit, leaves, branches, and roots. More than 120 triterpenoids have been identified in ZJ and ZA, and have various biological activities. For example, betulinic and ursolic acids have anticancer, antioxidant, antibacterial and antiviral activities. ceanothic, alphitolic, and zizyberanalic acids possess anti-inflammatory activities. The MVA pathway is a synthetic pathway for triterpenoids in ZJ and ZA, and 23 genes of the MVA pathway are known to regulate triterpene synthesis in ZJ and ZA. In order to better understand the basic situation of triterpenoids in ZJ and ZA, this paper reviews the types, content dynamic changes, activities, pharmacokinetics, triterpenoid synthesis pathways, and the effects of domestication on triterpenoids in ZJ and ZA, and provides some ideas for the future research of triterpenoids in ZJ and ZA. In addition, there are many types of ZJ and ZA triterpenoids, and most of the studies on their activities are on lupane- and ursane-type triterpenes, while the activities of the ceanothane-type and saponin are less studied and need additional research.

Mycotoxins are one of the most important sources for the discovery of new pesticides and drugs because of their chemical structural diversity and fascinating bioactivity as well as unique novel targets. Here, the effects of four mycotoxins, fumagillin, mevastatin, radicicol, and wortmannin, on photosynthesis were investigated to identify their precise sites of action on the photosynthetic apparatus of Chlamydomonas reinhardtii. Our results showed that these four mycotoxins have multiple targets, acting mainly on photosystem II (PSII). Their mode of action is similar to that of diuron, inhibiting electron flow beyond the primary quinone electron acceptor (QA) by binding to the secondary quinone electron acceptor (QB) site of the D1 protein, thereby affecting photosynthesis. The results of PSII oxygen evolution rate and chlorophyll (Chl) a fluorescence imaging suggested that fumagillin strongly inhibited overall PSII activity; the other three toxins also exhibited a negative influence at the high concentration. Chl a fluorescence kinetics and the JIP test showed that the inhibition of electron transport beyond QA was the most significant feature of the four mycotoxins. Fumagillin decreased the rate of O2 evolution by interrupting electron transfer on the PSII acceptor side, and had multiple negative effects on the primary photochemical reaction and PSII antenna size. Mevastatin caused a decrease in photosynthetic activity, mainly due to the inhibition of electron transport. Both radicicol and wortmannin decreased photosynthetic efficiency, mainly by inhibiting the electron transport efficiency of the PSII acceptor side and the activity of the PSII reaction centers. In addition, radicicol reduced the primary photochemical reaction efficiency and antenna size. The simulated molecular model of the four mycotoxins’ binding to C. reinhardtii D1 protein indicated that the residue D1-Phe265 is their common site at the QB site. This is a novel target site different from those of commercial PSII herbicides. Thus, the interesting effects of the four mycotoxins on PSII suggested that they provide new ideas for the design of novel and efficient herbicide molecules.

Parkinson’s disease (PD) is characterized pathologically by abnormal aggregation of alpha-synuclein (α-Syn) in the brain and clinically by fine movement deficits at the early stage, but the roles of α-Syn and associated neural circuits and neuromodulator bases in the development of fine movement deficits in PD are poorly understood, in part due to the lack of appropriate behavioral testing paradigms and PD models without motor confounding effects. Here, we coupled two unique behavioral paradigms with two PD models to reveal the following: (i) Focally injecting α-Syn fibrils into the dorsolateral striatum (DLS) and the transgenic expression of A53T-α-Syn in the dopaminergic neurons in the substantia nigra (SN, PITX3-IRES2-tTA/tetO-A53T mice) selectively impaired forelimb fine movements induced by the single-pellet reaching task. (ii) Injecting α-Syn fibers into the SN suppressed the coordination of cranial and forelimb fine movements induced by the sunflower seed opening test. (iii) Treatments with the adenosine A2A receptor (A2AR) antagonist KW6002 reversed the impairment of forelimb and cranial fine movements induced by α-Syn aggregates in the SN. These findings established a causal role of α-Syn in the SNc-DLS dopaminergic pathway in the development of forelimb and cranial fine movement deficits and suggest a novel therapeutic strategy to improve fine movements in PD by A2AR antagonists.

Abstract Introduction Transcriptomic divergence drives plant ecological adaptation. Upland rice is differentiated in drought tolerance from lowland rice during its adaptation to the drought‐prone environment. They provide a good system to learn the evolution of drought tolerance in rice. Methods and Results We estimate morphological differences between the two rice ecotypes under well‐watered and drought conditions, as well as their genetic and transcriptomic divergences by the high‐throughput sequencing. Upland rice possesses higher expression diversity than lowland rice does. Thousands of genes exhibit expression divergences between the two rice ecotypes, which contributes to their morphological differences in drought tolerance. These transcriptomic divergences contribute to drought adaptation of upland rice during its domestication. Mutations in transcriptional regulatory regions, which cause presence and absence of cis‐elements, are the cause of expression divergence. About 15.3% transcriptionally selected genes also receive sequence‐based selection in upland or lowland ecotype. Some highly differentiated genes promote the transcriptomic divergence between rice ecotypes via gene co‐expression network. In addition, we also detected transcriptomic trade‐offs between drought tolerance and productivity. Discussion Many key genes, which promote transcriptomic adaptation to drought in upland rice, have great prospective in breeding water‐saving and drought‐resistant rice. Meanwhile, appropriate strategies are required in breeding to overcome the potential transcriptomic trade‐off.

High-phosphorus diet (HPD) reduces lipid deposition and significantly influences lipid metabolism. However, the relevant mechanism is unknown. Herein, using widely-cultured teleost tilapia Oreochromis niloticus as the experimental animals, we found that HPD and Pi incubation reduced triglyceride (TG) content (P ≤ 0.05), suppressed lipogenesis, activated AMP-activated protein kinase (AMPK) pathway and autophagy (P ≤ 0.05), and increased fatty acid β-oxidation and lipolysis in tilapia liver and hepatocytes (P ≤ 0.05). Our further investigation indicated that Pi treatments activated the lipophagy and facilitated mitochondrial fatty acid β-oxidation, and according reduced TG deposition (P ≤ 0.05). Mechanistically, phosphorus increased the AMPKα1 phosphorylation level at S496 and Beclin1 phosphorylation at S90, and Beclin1 phosphorylation by AMPKα1 was required for phosphorus-induced lipophagy and lipolysis. Our study revealed a mechanism for Beclin1 regulation and autophagy induction in response to high-phosphorus diet, and provided novel evidences for the link between dietary phosphorus addition and lipolytic metabolism via the AMPK/Beclin1 pathway. Our results also suggested that AMPK should be the potential target for the prevention and control of lipid metabolic disorders. Overall, these results suggested that HPD reduced hepatic lipid deposition by activating AMPK pathway and Beclin1 phosphorylation levels to activate lipophagy, which provided potential targets for the prevention and control of fatty liver in fish.

Increasing dietary replacement levels of fish meal by alternative plant proteins are of value for aquaculture. Here, a 10-week feeding experiment was undertaken to explore the effects of fish meal replacement by mixed plant protein (at a 2 : 3 ratio of cottonseed meal to rapeseed meal) on growth performance, oxidative and inflammatory responses, and mTOR pathway of yellow catfish Pelteobagrus fulvidraco. Yellow catfish (2.38±0.1 g, mean±SEM) were randomly divided into 15 indoors fiberglass tanks, 30 fish each tank, and fed five isonitrogenous (44% crude protein) and isolipidic (9% crude fat) diets with fish meal replaced by mixed plant protein at 0% (the control), 10% (RM10), 20% (RM20), 30% (RM30), and 40% (RM40), respectively. Among five groups, fish fed the control, and RM10 diets tended to have higher growth performance, higher protein content, and lower lipid content in livers. Dietary mixed plant protein substitute increased hepatic free gossypol content and damaged liver histology and reduced the serum total essential amino acids, total nonessential amino acids, and total amino acid contents. Yellow catfish fed the control, and RM10 diets tended to have higher antioxidant capacity. Dietary mixed plant protein replacement tended to promote proinflammatory responses and inhibited mTOR pathway. Based on the second regression analysis of SGR against mixed plant protein substitutes, the optimal replacement level of fish meal by mixed plant protein was 8.7%.

Cardiac symptoms or signs as the first manifestations in acute lymphoblastic leukemia patients are sporadically reported which lead to misdiagnosis or delayed diagnosis due to lack of clinical experience and improper diagnosis procedures. Here, we documented the clinical features, procedures of diagnosis, treatments, and outcomes from the so-far reported 30 lymphoblastic leukemia cases that initially presented as cardiac problems and provided management recommendations based on the experiences and lessons learned from these patients to help physicians avoid misdiagnosis and improper treatment.

Background. Adiponectin is a recognized antiatherogenic molecule; this study was aimed at clarifying the effects of adiponectin variants on lipid and adiponectin levels. Methods. By searching PubMed and Cochrane databases for studies published before March 31, 2022, a total of 86,610 individuals were included in the analysis. Results. Variants of rs2241766 and rs266729 were associated with decreased adiponectin and high-density lipoprotein cholesterol (HDL-C), as well as increased triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels. In contrast, the rs1501299 variant was correlated with increased adiponectin and HDL-C, as well as decreased TG, TC, and LDL-C levels. Subgroup analysis indicated that the significant effect of the rs2241766 and rs266729 variants on lipid profile was predominant in Chinese, while the significant effect of the rs1501299 variant on lipid profile was primarily in Caucasians. Moreover, a stronger effect of the rs2241766 and rs1501299 variants on LDL-C levels was observed in males, while a considerable effect of the rs266729 variant on LDL-C levels was observed in children. Conclusions. The present study indicated that Chinese with the rs2241766 and rs266729 variants were at high risk of dyslipidemia, atherosclerosis, or coronary artery disease (CAD). Males with the rs2241766 variant were at high risk of CAD. Children with the rs266729 variant had a high risk to develop dyslipidemia, atherosclerosis, and even early onset of CAD in the future. These findings are beneficial to clinical physicians to choose different management strategies for cardiovascular disease (CVD) prevention.

Abstract Background Recently, some studies claim that adipokines may modulate plasma lipids. More interestingly, the ADRB3 Trp64Arg polymorphism may regulate adipokines and play an essential role in lipids metabolism. This study aims to clarify the associations of ADRB3 Trp64Arg polymorphism with plasma adipokines and lipid levels. Methods Twenty-two studies (5527 subjects) and 121 studies (54,059 subjects) were respectively identified for the association analyses of adipokines and lipids. Standardized mean difference (SMD) and 95% confidence interval (CI) were used to estimate the strength of the Trp64Arg variant in adipokines and plasma lipids. All results were recalculated after eliminating the studies with heterogeneity. Results The carriers of the C allele (Arg at 64th position was encoded by the C allele) had higher levels of leptin and lower levels of adiponectin than the non-carriers. The carriers of the C allele had higher levels of triglycerides (TG), total cholesterol (TC), and lower levels of high-density lipoprotein cholesterol (HDL-C) than the non-carriers. Subgroup analysis certified an ethnicity (Asians), disease status (obesity), and gender (females) specific association. Sensitivity analysis indicated that the analysis results were robust and stable. Meta-regression indicated that obesity was related to adiponectin. Conclusions The C allele carriers of Trp64Arg polymorphism had a slight but significant influence on lipid levels, and the remarkable effects specific existed in obese Asian women. The associations of Trp64Arg polymorphism with dyslipidemia may partly be mediated by the effect of this polymorphism on adipokines. The association of Trp64Arg polymorphism with obesity may partly be mediated by the effect of this polymorphism on adipokines. The C allele carriers had abnormal levels of adipokines and lipids, and it indicated that the Trp64Arg polymorphism might represent a genetic risk factor for coronary artery disease (CAD).

The study to obtain a sound joint between aluminum and steel is rather challenging due to the large mismatch in thermal properties and the formation of brittle IMCs, especially for press-hardened steel attributing to its martensite microstructure. In this present study, dissimilar joining of 5052 aluminum and press-hardened steel was comprehensively explored by employing laser offset welding without any fillers and interlayers. The influence of laser offset on welding appearance and mechanical properties was evaluated. The microstructure analysis, bonding mechanism, and fracture behavior were identified and characterized by means of optical microscope (OM), scanning electron microscope (SEM), energy-dispersive X-ray spectrometer (EDS), and X-ray diffraction (XRD). The satisfactory welding appearance and mechanical property of 129.6 MPa was obtained at the laser offset of 0.2 mm. The interface microstructure was composed of continuous Fe2Al5, acicular Fe4Al13 and islands IMCs. In addition, micro cracks could be initiated spontaneously in Fe2Al5 layer due to the residual stress, whereas a consecutive crack seems be induced by a micro pore defect. No matter what the fracture mode was during tensile test, the fracture surface was localized at the welded interface.

Abstract Background Excessive dietary fat intake induces lipid deposition and contributes to the progress of nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanisms are still unclear. Methods Yellow catfish were given two experimental diets with dietary lipid levels of 11.3 and 15.4%, respectively, for 56 days, and the contents of triglyceride (TG), nonesterified free fatty acids (NEFA) and bile acid (BA), RNA-seq, enzymatic activities and mRNA expression were deteremined in the liver tissues. Hepatocytes from yellow catfish liver tissues were isolated and cultured. Fatty acids (FA) (palmitic acid: OA, oleic acid =1:1), pathway inhibitors (MA, autophagy inhibitor; guggulsterone, FXR inhibitor) and agonist (rapamyicn, autophagy agonist; GW4064, FXR agonist) were used to incubate the cells. TG and NEFA contents, ultrastructural observation, autophagic vesicles and intracellular LD,apoptosis,western blot and Co-IP, and Immunofluorescence analysis, enzymatic activities and Q-PCR were decided. Results Using RNA sequencing, we found that high fat diets induced changes in expression of many genes associated with the pathways of lipid metabolism and autophagy. The mRNA profiles of the differentially expressed genes (DEG) indicated that high dietary fat-induced lipid deposition was predominantly influenced by the inhibition of autophagy. Using primary hepatocytes, we found that fatty acids (FA) suppressed autophagy, which in turn reduced cellular free FA level by decreasing triglyceride (TG) breakdown. Moreover, our study indicated that farnesoid X receptor (FXR)-cyclic AMP-responsive element-binding protein (CREB) axis was the pivotal physiological switch regulating FA-induced changes of autophagy and lipid metabolism, which represented cellular defenses against FA-induced lipotoxicity. Conclusion This discovery may provide new targets for treating pathological changes involved in the dysfunction of autophagy and metabolism, including NAFLD. Video Abstract Graphical abstract

Based on the device physics, a mobility model for organic thin-film transistors (OTFTs) is presented considering temperature and contact resistance. As a function of the surface potential, the mobility model including hopping mechanism is able to explain the dependence of temperature and gate bias. The contact resistance is also considered in order to extract the correct mobility. Furthermore, with the assumption that the trapped carrier concentration dominates Poisson's equation, and combining the mobility model, a DC compact model accounting for contact resistance and temperature is proposed suitable for the temperature scaling from 83 to 295K. Through the extensive comparisons between the model results and the numerical iteration or experimental data, the validity of the mobility and current models is strongly supported.

High-fat diets (HFD) lead to impairment of chylomicrons (CMs) assembly and adversely influence intestinal lipid homeostasis. However, the mechanisms of HFD impairing CMs assembly have yet to be fully understood. Additionally, although choline, as a lipid-lowering agent, has been widely used and its deficiency has been closely linked to non-alcoholic steatohepatitis (NASH), the contribution of choline by functioning as a methyl donor in alleviating HFD-induced intestinal lipid deposition is unknown. Thus, this study was conducted to determine the mechanism of HFD impairing CMs assembly and also tested the effect of choline acting as a methyl donor in this process. To this end, in this study, four diets (control, HFD, choline and HFD + choline diet) were fed to yellow catfish for 10 weeks in vivo and their intestinal epithelial cells were isolated and incubated for 36 h in fatty acids (FA) with or without choline solution combining si-perk transfection in vitro. The key findings from this study as follows: (1) HFD caused impairment of CMs assembly main by unfolded protein response (UPRer). HFD activated perk and then induced UPRer, which led to endoplasmic reticulum dysfunction and further impaired CMs assembly via protein–protein interactions between Perk and Apob48. (2) Choline inhibited the transcriptional expression level of perk via activating the −211 CpG methylation site, which initiated the subsequent ameliorating effect on HFD-impaired CMs assembly and intestinal lipid dysfunction. These results provide a new insight into direct crosstalk between UPRer and CMs assembly, and also emphasize the critical contribution of choline acting as a methyl donor and shed new light on choline-deficient diet-induced NASH.

Here, we characterized the function of ctr1, ctr2 and atox1 promoters in yellow catfish Pelteobagrus fulvidraco, a common freshwater teleost in Asian countries. We obtained 1359 bp, 1842 bp and 1825 bp sequences of ctr1, ctr2 and atox1 promoters, and predicted key transcription factor binding sites on their promoters, including MRE, SREBP1, NRF2, KLF4 and STAT3. Cu differentially influenced the activities of ctr1, ctr2 and atox1 promoters from different regions. We found that the −326/−334 bp and −1232/−1240 bp locus in the atox1 promoter were functional NRF2 binding sites, which negatively controlled the activity of the atox1 promoter. The −91/−100 bp locus in the ctr1 promoter and −232/−241 bp and −699/−708 bp locus in the atox1 promoter were functional SREBP1 binding sites, which positively controlled the activities of ctr1 and atox1 promoters. Cu inhibited the NRF2 binding ability to the atox1 promoter, but promoted the SREBP1 binding ability to the ctr1 and atox1 promoters. Dietary Cu excess significantly down-regulated hepatic mRNA and total protein expression of CTR1, CTR2 and ATOX1 of yellow catfish, compared to the adequate dietary Cu group. The subcellular localization showed that CTR1 was mainly localized on the cell membrane, CTR2 in the cell membrane and the lysosome, and ATOX1 in the cytoplasm. In conclusion, we demonstrated the regulatory mechanism of three Cu transporters at the transcription levels, and found the functional NRF2 and SREBP1 response elements in ctr1, ctr2 and atox1 promoters, which provided new insights into their roles in the regulation of Cu homeostasis in fish.

Biological herbicides have received much attention due to their abundant resources, low development cost, unique targets and environmental friendliness. This study reveals some interesting effects of mycotoxin cytochalasin A (CA) on photosystem II (PSII). Our results suggested that CA causes leaf lesions on Ageratina adenophora due to its multiple effects on PSII. At a half-inhibitory concentration of 58.5 μΜ (I50, 58.5 μΜ), the rate of O2 evolution of PSII was significantly inhibited by CA. This indicates that CA possesses excellent phytotoxicity and exhibits potential herbicidal activity. Based on the increase in the J-step of the chlorophyll fluorescence rise OJIP curve and the analysis of some JIP-test parameters, similar to the classical herbicide diuron, CA interrupted PSII electron transfer beyond QA at the acceptor side, leading to damage to the PSII antenna structure and inactivation of reaction centers. Molecular docking model of CA and D1 protein of A. adenophora further suggests that CA directly targets the QB site of D1 protein. The potential hydrogen bonds are formed between CA and residues D1-His215, D1-Ala263 and D1-Ser264, respectively. The binding of CA to residue D1-Ala263 is novel. Thus, CA is a new natural PSII inhibitor. These results clarify the mode of action of CA in photosynthesis, providing valuable information and potential implications for the design of novel bioherbicides.

Background: The studies of miRNAs are vibrant and remain at the forefront in the cardiovascular system. Emerging studies indicate that the genetic polymorphisms of the miRNA gene may affect lipid metabolism; this study aims to clarify the specific correlations between the rs2910164 and rs3746444 polymorphisms and lipid levels.Methods and Results: A comprehensive search of literature was performed from December 31, 2020, to May 31, 2021, by searching of the PubMed and the Cochrane databases. The standardized mean difference (SMD) and 95% confidence interval (CI) were used to evaluate the differences in lipid levels between the genotypes. rs2910164, a functional polymorphism in the miRNA-146a gene, was associated with increased triglycerides (TG) (SMD = 0.35, 95% CI = 0.15–0.54, p < 0.001), total cholesterol (TC) (SMD = 0.43, 95% CI = 0.16–0.70, p < 0.001), and low-density lipoprotein cholesterol (LDL-C) (SMD = 0.37, 95% CI = 0.11–0.63, p = 0.01) as well as decreased high-density lipoprotein cholesterol (HDL-C) (SMD = −0.27, 95% CI = −0.47−0.07, p = 0.01) levels. rs3746444, a functional polymorphism in the miRNA-499a gene, was only correlated with decreased TG (SMD = −0.09, 95% CI = −0.17−0.01, P = 0.03) levels.Conclusions: The miRNA-146a rs2910164 polymorphism is significantly associated with atherogenic dyslipidemia.