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We prospectively investigated the neurological development in infants born from mothers treated with telbivudine (LdT) in the third trimester for prevention of hepatitis B virus (HBV) mother-to-infant transmission. Mothers with high HBV load were assigned to either the LdT group (n = 81, 600 mg of LdT each day from gestational week 28 to delivery) or the Control group (n = 39, untreated). Their infants were followed for 36 months to assess physical and neurological developments with Gesell Developmental Schedule tools. At 12 months after birth, the mean scores in the LdT group for gross motor, fine motor, adaptive, linguistic, and personal social domains were similar to those in the Control group. At 36 months, infants in the LdT group had higher mean scores for gross motor than the Control group (98.42 ± 9.69 vs. 94.54 ± 7.48, P = 0.03). In the LdT group, the rates of normal development were higher for gross motor (96.30% vs. 82.05% P = 0.01) and lower for adaptive (74.07% vs. 92.31% P = 0.02). Multivariate regression analyses showed that exposure to LdT during pregnancy was independently associated with infant’s development in gross motor (OR 6.49, 95% CI 1.37–30.20, P = 0.02) and adaptive (OR 0.18, 95% CI 0.05–0.71, P = 0.01) at 36 months. These results suggest that prenatal LdT exposure might affect neurological development in long-term observation. Abbreviations: LdT: telbivudine; HBV: hepatitis B virus; HBsAg: hepatitis B surface antigen; HBeAg: hepatitis Be antigen; HbsAb: hepatitis B surface antibody; ALT: alanine aminotransferase; NA: nucleoside/nucleotide analog; LAM: lamivudine; MTCT: mother-to-child transmission; GDS: Gesell Developmental Schedule; OR: odds ratio; CI: confidence interval; DQ: developmental quotient; RMB: renminbi; BMI: body mass Index; HBIG: hepatitis B immunoglobulin.

BACKGROUND Many patients with primary membranous nephropathy have severe proteinuria unresponsive to optimized renin-angiotensin-aldosterone system inhibitors (RAASi). We evaluated the efficacy and safety of hydroxychloroquine as an adjunctive agent in membranous nephropathy (MN) treatments. METHODS We prospectively recruited 126 patients with biopsy-proven primary membranous nephropathy and urinary protein 1-8 g/day while receiving optimized RAASi treatment for ≥ 3 months and well-controlled blood pressure. Forty-three patients received hydroxychloroquine and RAASi (hydroxychloroquine-RAASi group), and 83 patients received RAASi alone (RAASi group). Treatment responses, including proteinuria reduction, complete and partial remission rates, and autoantibody against phospholipase A2 receptor (anti-PLA2R) levels, were compared between the two groups at 6 months and over the long term. RESULTS At 6 months, the effective response rate (proteinuria reduction > 30%) (57.5% vs. 28.9%, P = 0.002), clinical remission rate (35.0% vs. 15.7%, P = 0.015), and percentage change in proteinuria (- 51.7% vs. - 21.9%, P

The South American tomato pinworm, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), has invaded most Afro-Eurasian countries and is threatening worldwide tomato production. Various strategies have been developed and implemented to manage this pest. Here, we present a timely review on the up-to-date development and practical implementation of integrated pest management (IPM) programs for tomato crops across different world regions infested by T. absoluta. While insecticide resistance is a growing concern, biological control via releasing or conserving arthropod natural enemies and sex pheromone-based biotechnical control are the most successful management practices. Agronomic control-related research is an emerging area where the soil fertilization and/or irrigation, as well as breeding of resistant cultivars, has the potential to enhance IPM effectiveness. Grower survey responses in the native areas (i.e., South America), early-invaded areas (i.e., first report between 2006 and 2012) and newly invaded areas (i.e., first report after 2012) showed that the control programs evolved along with the areas and time since invasion. Growers in the early-invaded areas shifted more rapidly from chemical control to biological control compared to those from the native area. In all concerned regions, the pest control failure risk following chemical insecticide applications and the high cost associated with either biological or biotechnical control methods have been the greatest concerns for growers. The information gathered from the native and/or early-invaded areas may help achieve a more effective management in newly invaded areas. Lastly, researchers are expected to break the bottlenecks of some key issues that would enable lowering application cost of novel biorational alternative management options.

Bacterial endophthalmitis is a rare intraocular infection, and prompt administration of intravitreal antibiotics is crucial for preventing severe vision loss. The retrospective study is to investigate the in vitro susceptibility to the antibiotics vancomycin, amikacin, and ceftazidime of bacterial endophthalmitis isolates in specimens at a tertiary referral center from January 1996 to April 2019 in Taiwan. Overall, 450 (49.9%) isolates were gram positive, 447 (49.6%) were gram negative, and 4 (0.4%) were gram variable. In gram-positive isolates, coagulase-negative staphylococci were the most commonly cultured bacteria (158, 35.1%), followed by streptococci (100, 22.2%), enterococci (75, 16.7%), and Staphylococcus aureus (70, 15.6%). In gram-negative isolates, they were Klebsiella pneumoniae (166, 37.1%) and Pseudomonas aeruginosa (131, 29.3%). All gram-positive organisms were susceptible to vancomycin, with the exception of one Enterococcus faecium isolate (1/450, 0.2%). Of the gram-negative isolates, 96.9% and 93.7% were susceptible to ceftazidime and amikacin, respectively. Nine isolates (9/447, 2.0%) were multidrug-resistant gram-negative bacteria, comprising Klebsiella pneumoniae (4/164, 2.4%), Acinetobacter baumannii (2/3, 67%), and Stenotrophomonas maltophilia (3/18, 17%). In conclusion, in vitro susceptibility testing revealed that vancomycin remains the suitable antibiotic treatment for gram-positive endophthalmitis. Ceftazidime and amikacin provide approximately the same degree of gram-negative coverage. Multidrug-resistant bacterial endophthalmitis was uncommon.

Otolith microstructural features and morphological development of larval and juvenile fish are important for studying the early life history of fish. In this study, the analysis of otolith features was performed on Squalidus argentatus laboratory-reared larvae and juveniles (0 to 40 days post-hatching or dph) collected as eggs in the Laibin section of the Pearl River (South China) from April to August 2020. According to the otolith development analysis, there was a corresponding relationship between the development of otoliths and the ontogenesis of fish, in which the shape of otoliths had a greater change in the post-flexion larval stage corresponding to the formation period of each fin. Observations of the microstructural features suggested that lapilli were the most suitable otoliths for age determination and increment deposition rate validation among the three pairs of otoliths. The result of a regression analysis of the number of lapilli increments on age indicated that otolith growth increments were deposited daily and the first increment was deposited at 3 dph. Our results support the usage of otolith increment deposition rate when assessing hatching dates and daily growth for wild S. argentatus at 40 dph when environmental conditions are comparable to those described in this study.

ULK1 (unc-51 like autophagy activating kinase) has a central role in initiating macroautophagy/autophagy, a process that contributes to atherosclerosis and neointima hyperplasia, or excessive tissue growth that leads to vessel dysfunction. However, the role of ULK1 in neointima formation remains unclear. We aimed to determine how Ulk1 deletion affected neointima formation and to investigate the underlying mechanisms. We measured autophagy activity, vascular smooth muscle cell (VSMC) migration and neointima hyperplasia in cultured VSMCs and ligation-injured mouse carotid arteries from male wild-type (WT, C57BL/6 J) and VSMC-specific ulk1 knockout (ulk1 KO) mice. Carotid artery ligation in WT mice increased ULK1 protein expression, and concurrently increased autophagic flux and neointima formation. Treating human aortic smooth muscle cells (HASMCs) with PDGF (platelet derived growth factor) increased ULK1 expression, activated autophagy, and promoted cell migration. Further, smooth muscle cell-specific deletion of Ulk1 suppressed autophagy, inhibited VSMC migration, and impeded neointima hyperplasia. Mechanistically, Ulk1 deletion inhibited autophagic degradation of histone acetyltransferase protein KAT2A/GCN5 (K[lysine] acetyltransferase 2A), resulting in accumulation of KAT2A that directly acetylated TUBA/α-tubulin and subsequently increased protein levels of acetylated TUBA. The acetylation of TUBA increased microtubule stability and inhibited VSMC directional migration and neointima formation. Finally, local transfection of Kat2a siRNA decreased TUBA acetylation and prevented the attenuation of vascular injury-induced neointima formation in ulk1 KO mice. These findings suggest that Ulk1 deletion inhibits neointima formation by reducing autophagic degradation of KAT2A and increasing TUBA acetylation in VSMCs.Abbreviations: ACTA2/α-SMA: actin, alpha 2, smooth muscle, aorta; ACTB: actin beta; ATAT1: alpha tubulin acetyltransferase 1; ATG: autophagy related; BECN1: beclin 1; BP: blood pressure; CAL: carotid artery ligation; CQ: chloroquine diphosphate; EC: endothelial cells; EEL: external elastic layer; FBS: fetal bovine serum; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; HASMCs: human aortic smooth muscle cells; HAT1: histone acetyltransferase 1; HDAC: histone deacetylase; IEL: inner elastic layer; IP: immunoprecipitation; KAT2A/GCN5: K(lysine) acetyltransferase 2A; KAT8/hMOF: lysine acetyltransferase 8; MAP1LC3: microtubule associated protein 1 light chain 3; MYH11: myosin heavy chain 11; PBS: phosphate-buffered saline; PDGF: platelet derived growth factor; PECAM1/CD31: platelet and endothelial cell adhesion molecule 1; RAC3: Rac family small GTPase 3; SIRT2: sirtuin 2; SPP1/OPN: secreted phosphoprotein 1; SQSTM1/p62: sequestosome 1; TAGLN/SM22: transgelin; TUBA: tubulin alpha; ULK1: unc-51 like autophagy activating kinase; VSMC: vascular smooth muscle cell; VVG: Verhoeff Van Gieson; WT: wild type.

Uromodulin (UMOD) can bind complement factor H (cFH) and inhibit the activation of complement alternative pathway (AP) by enhancing the cofactor activity of cFH on degeneration of C3b. UMOD, an N‐glycans‐rich glycoprotein, is expressed in thick ascending limb of Henle's loop where the epithelia need to adapt to gradient change of pH and ion concentration. ELISA‐based cofactor activity of cFH and erythrocytes haemolytic assay was used to measure the impact of native and de‐glycosylated UMOD on the functions of cFH. The binding assay was performed under different pH and ion concentrations, using ELISA. The levels of sialic acid on UMOD, from healthy controls and patients with chronic kidney disease (CKD), were also detected by lectin‐ELISA. It was shown that removal of glycans decreased the binding between UMOD and cFH and abolished the ability of enhancing C3b degradation. In acidic condition, the binding became stronger, but it reduced as sodium concentration increased. A significant decrease of α‐2,3 sialic acids on UMOD was observed in CKD patients compared with that of healthy individuals. The sialic acids on UMOD, local pH and sodium concentration could impact the binding capacity between UMOD and cFH and thus regulate the activation of complement AP.

—The phylogenetic relationships among 11 out of the 12 genera of the angiosperm family Styracaceae have been largely resolved with DNA sequence data based on all protein-coding genes of the plastome. The only genus that has not been phylogenomically investigated in the family with molecular data is the monotypic genusParastyrax, which is extremely rare in the wild and difficult to collect. To complete the sampling of the genera comprising the Styracaceae, examine the plastome composition ofParastyrax, and further explore the phylogenetic relationships of the entire family, we sequenced the whole plastome ofP.laceiand incorporated it into the Styracaceae dataset for phylogenetic analysis. Similar to most others in the family, the plastome is 158189 bp in length and contains a large single-copy region of 88085 bp and a small single-copy region of 18540 bp separated by two inverted-repeat regions of 25781 bp each. A total of 113 genes was predicted, including 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. Phylogenetic relationships among all 12 genera of the family were constructed with 79 protein-coding genes. Consistent with a previous study,Styrax,Huodendron, and a clade ofAlniphyllum+Bruinsmiawere successively sister to the remainder of the family.Parastyraxwas strongly supported as sister to an internal clade comprising seven other genera of the family, whereasHalesiaandPterostyraxwere both recovered as polyphyletic, as in prior studies. However, when we employed either the whole plastome or the large- or small-single copy regions as datasets,Pterostyraxwas resolved as monophyletic with 100% support, consistent with expectations based on morphology and indicating that non-coding regions of the Styracaceae plastome contain informative phylogenetic signal. ConverselyHalesiawas still resolved as polyphyletic but with novel strong support.

For highly conserved mammalian protein, chicken is a suitable immune host to generate antibodies. Monoclonal antibodies have been successfully targeted with immunity checkpoint proteins as a means of cancer treatment; this treatment enhances tumor-specific immunity responses through immunoregulation. Studies have identified the importance of B7-H4 in immunoregulation and its use as a potential target for cancer treatment. High levels of B7-H4 expression are found in tumor tissues and are associated with adverse clinical and pathological characteristics. Using the phage display technique, this study isolated specific single-chain antibody fragments (scFvs) against B7-H4 from chickens. Our experiment proved that B7-H4 clearly induced the inhibition of T-cell activation. Therefore, use of anti-B7-H4 scFvs can effectively block the exhaustion of immunity cells and also stimulate and activate T-cells in peripheral blood mononuclear cells. Sequence analysis revealed that two isolated scFv S2 and S4 have the same VH complementarity-determining regions (CDRs) sequence. Molecule docking was employed to simulate the complex structures of scFv with B7-H4 to analyze the interaction. Our findings revealed that both scFvs employed CDR-H1 and CDR-H3 as main driving forces and had strong binding effects with the B7-H4. The affinity of scFv S2 was better because the CDR-L2 loop of the scFv S2 had three more hydrogen bond interactions with B7-H4. The results of this experiment suggest the usefulness of B7-H4 as a target for immunity checkpoints; the isolated B7-H4-specific chicken antibodies have the potential for use in future cancer immunotherapy applications.

Plants are vulnerable to heat stress, especially during reproductive development. The heat shock response (HSR) in the cytosol and nucleus, as well as the unfolded protein response (UPR) in the endoplasmic reticulum (ER), are two mechanisms that enable plants to survive heat stress. Excessive heat or ER stresses lead to cell death when the UPR cannot repair stress damage, but the means by which cell survival or death is determined remains unclear. In this study, we used a genome-wide association study (GWAS) to identify that a cluster of five Immune-associated nucleotide-binding protein (IAN) genes (IAN2 to IAN6) is responsible for variation in heat tolerance at the reproductive stage in Arabidopsis thaliana. These IAN genes have both unique and overlapping functions in the negative regulation of heat tolerance, and their loss of function singly or in combination confers increased heat tolerance, measured by a lower number of barren siliques and a higher seedling survival rate under heat. The loss of rice IAN1 gene function also leads to enhanced heat tolerance, suggesting a conserved function of plant IANs. Transcriptome analysis revealed enhanced expression of HSR and UPR genes, as well as reduced cell death, under heat and ER stress in the mutant of IAN6, a major effect member in Arabidopsis. Furthermore, the IAN proteins were found to promote cell death induced by heat stress, ER stress, and cell death-inducing molecules. Thus, the Arabidopsis IAN genes repress heat tolerance, probably through the HSR and UPR and by enhancing the cell death pathway. The IAN2 to IAN6 proteins are partially localized to the ER, suggesting a direct role in the UPR and UPR-mediated cell death. In addition, a natural IAN6 variant from more heat-tolerant Arabidopsis accessions confers greater heat tolerance and induces less cell death compared with the natural variant from less heat-tolerant accessions. The heat-tolerant IAN6 variant is associated with a higher maximum temperature of the warmest month at its collection sites compared with the heat-sensitive variant. Taken together, these results reveal an important role of Arabidopsis IAN2 to IAN6 genes in the regulation of the HSR, UPR, and cell death, and suggest that their natural variations have adaptive functions in heat tolerance.

Spotted fever group rickettsiae, mainly maintained and transmitted by ticks, are important etiological agents of (re)emerging zoonotic diseases worldwide. It is of great significance to investigate spotted fever group rickettsiae in ticks in different areas for the prevention and control of rickettsioses. In this study, a total of 305 ticks were collected from wild and domestic animals in Chongqing, Guizhou, Yunnan, and Guangxi provinces of southwestern China during 2017–2019 and examined for the presence of spotted fever group rickettsiae by PCR with primers targeting the partial gltA, ompA, rrs, and htrA genes. Results showed that two spotted fever group rickettsiae species, including the pathogenic Candidatus Rickettsia jingxinensis (Rickettsiales: Rickettsiaceae) and a potential novel species Rickettsia sp. sw (Rickettsiales: Rickettsiaceae), were identified. The Ca. R. jingxinensis sequences were recovered from Rhipicephalus microplus (Ixodida: Ixodidae) and Haemaphysalis longicornis (Ixodida: Ixodidae) ticks and phylogenetically clustered with previous Ca. R. jingxinensis, Ca. R. longicornii (Rickettsiales: Rickettsiaceae), and Rickettsia sp. XY118 (Rickettsiales: Rickettsiaceae) strains. Rickettsia sp. sw was detected in Amblyomma geoemydae (Ixodida: Ixodidae) and Rh. microplus. Interestingly, as far as we know, this was the first report of Rickettsia (Rickettsiales: Rickettsiaceae) in A. geoemydae. Phylogenetic analyses indicated that this potential novel species was closely related to R. aeschlimannii (Rickettsiales: Rickettsiaceae) with gltA and ompA genes and grouped in a cluster composed of R. montanensis (Rickettsiales: Rickettsiaceae), R. raoultii (Rickettsiales: Rickettsiaceae), R. aeschlimannii, R. massiliae (Rickettsiales: Rickettsiaceae), and R. rhipicephali (Rickettsiales: Rickettsiaceae) with htrA, while formed a separate clade with rrs. The pathogenicity of Rickettsia sp. sw should be further confirmed. These results expand the knowledge of the geographical distribution and vector distribution of spotted fever group rickettsiae in China and are useful for assessing the potential public health risk.

Increasing number of resistant bacteria have emerged with the overuse of antibiotics, which indicates that the bacterial infection has become a global challenge. Furthermore, the pollution of antibiotics to the environment has become a serious threat to public health. It is known that toxins produced by bacteria are the main cause of bacterial infections. Photothermal therapy is an effective antibacterial approach. However, the photothermal reagents cannot eliminate bacterial toxins, and even some anti-bacterial materials are toxic. Here, we synthesized a biomimetic recycled nanoparticle, red blood cell (RBC) membrane-coated Fe3O4 nanoparticles (RBC@Fe3O4), as an antibacterial agent. The RBC@Fe3O4 nanoparticles act as nano-sponges to trap toxins and then kill them all with a photothermal effect. We can describe this process simply as a battle between two armies. Our strategy is to disarm the "enemy" so that we can easily kill the "enemy" who has no power, which results in enhancing the bactericidal efficacy. The toxin of methicillin-resistant Staphylococcus aureus (MRSA) was absorbed by RBC@Fe3O4in vitro. In addition, in vivo studies proved that the RBC@Fe3O4 nanoparticles confer obvious survival benefits against toxin-induced lethality by absorbing the toxin of MRSA. Furthermore, using a mouse model of MRSA wound infection, the RBC@Fe3O4 nanoparticles with laser irradiation were found to have a superior wound-healing effect. Simultaneously, the RBC@Fe3O4 nanoparticles could be recycled in a simple way without affecting the bactericidal efficacy. The highly biocompatible and recyclable RBC@Fe3O4 biomimetic nanoparticles based on photothermal therapy and bacterial toxin adsorption strategy are promising for treating bacterial infections.

Tumor metastasis is the main reason for the death of most cancer patients. C-X-C chemokine receptor type 4 (CXCR4) has been demonstrated to be overexpressed in numerous types of cancer. CXCR4 selectively binds with stromal cell-derived factor 1 (SDF1), also known as C-X-C family chemokine ligand 12 (CXCL12) (CXCL12/SDF-1), which induced tumor proliferation and metastasis. Recently, the use of conventional cancer treatments had some limitation; bacteria treatment for cancer becomes a trend that overcomes these limitations. Plenty of studies show that Salmonella has anti-tumor and anti-metastatic activity. The current study aimed to investigate Salmonella suppresses CXCR4 protein expression and tumor cell migration ability in B16F10 melanoma and LL2 lung carcinoma cells. Salmonella reduced CXCR4 protein expression through downregulating Protein Kinase-B (Akt)/Mammalian Target of Rapamycin (mTOR) signaling pathway. In cells transfected with constitutively active Akt plasmids, a reverse effect of Salmonella-induced inhibition of CXCR4 was observed. Tumor cells have chemotactic response to CXCL12 in migration assay, and we found that Salmonella reduced tumor chemotactic response after CXCL12 treatment. The C57BL/6 mice were intravenously injected with B16F10 and LL2 cells pre-incubated with or without Salmonella, the tumor size and lung weight of Salmonella group had obviously decreased, indicating anti-metastatic effect that confirmed the findings from the in vitro experiments.

A novel species, Distoseptispora longispora, from submerged wood in Yunnan Province, China, is described and illustrated. The fungus is characterized by macronematous, mononematous, septate conidiophores with monoblastic, integrated, determinate, terminal conidiogenous cells that produce acrogenous, solitary, obclavate, elongated, distoseptate conidia. SSU-ITS-LSU sequence analyses were used to infer the phylogenetic relationship between D. longispora and related species. Both molecular analyses and morphological data well support D. longispora as an independent taxon. A key to Distoseptispora species is provided.

The extension of lifespan by means of calorie restriction (CR) is one of the most replicable mechanisms across a range of different taxa. However, the effects of this on the next generation are less studied due to the complexities associated with such an experiment. In this study, the effects of CR and ad libitum (AL) feeding on lifespan, duration of ovipositional stages, and fecundity of a predatory mite, Neoseiulus cucumeris were investigated. The egg volume, sex ratio, and survival rate of the offspring were then compared across the different treatments. The three treatments were: (1) 40 prey Tyrophagus putrescentiae eggs per day representing the AL treatment; (2) 10 eggs per day representing medium CR; and (3) 5 eggs per day being high CR. To assess for transgenerational effects, the eggs produced under the three different treatments were fed AL and reared until adulthood or death. Mothers under the medium CR treatment had a lifespan that almost doubled the lifespan of mothers fed AL. Contrastingly, a higher reproductive rate was seen in mothers under AL, which also had a significantly higher total fecundity when compared with both CR treatments. The AL mothers had a shorter gestational period and produced larger eggs. There was no difference between the sex ratio of offspring for the medium CR and AL treatments. These results indicate the different effects of the two levels of CR and highlight the trade-offs that are accompanied with a longer lifespan due to caloric restriction.

Background: Forkhead transcription factor 3 (FOXP3) is a key molecule for the development of regulatory T cell. Recent studies showed that FOXP3 was also expressed in tumor cells. This study is designed to identify the expression of FOXP3 and its pathogenesis in hepatocellular carcinoma (HCC).

The association between high-sensitivity C-reactive protein (hs-CRP) and chronic kidney disease remains controversial and long-term longitudinal studies are limited. We aim to investigate the impact of single and persistent elevation of hs-CRP on kidney outcomes. Our study was based on a subgroup of patients with hyperglycemia from the Kailuan cohort. Patients were divided into three groups according to two consecutive hs-CRP levels: (1) no elevation (twice hs-CRP

Heat stress negatively affects wheat production in many regions of the world. At present, sensitivity to heat stress remains one of the least understood aspects of wheat genetics and breeding, and measures for preventing heat stress are understudied. In this study, we used three cultivars of winter wheat (GY2018, SL02-1 and SY20) to evaluate the effect of heat stress at different days after anthesis (DAA) on yield and quality. Heat stability of the cultivars were analyzed and evaluated for the effects of two kinds of regulators on wheat under heat stress conditions. Heat treatment at 7 DAA led to the most substantial reduction in yield while GY2018 had the best heat stability with respect to yield, and demonstrated the most positive effects on several quality traits including protein content, sedimentation volume and glutenin and gliadin contents. Heat treatment at 14 DAA had the least reduction in yield, while SY20 had the best heat stability with respect to yield and heat treatment had minimal effects on quality. Heat treatment at 21 DAA had only a limited effect on yield, while SL02-1 had the best heat stability with respect to yield, but it showed the most negative effects on quality. Stable time at 14 DAA and protein content at 21 DAA can be used as indicators for detecting the stability of quality under heat stress. Among the three studied cultivars, SY20 was the most sensitive to heat stress with the stable time decreasing from 26.4 to 9.1 min, a higher sedimentation volume at 7 DAA, and a lower γ-gliadin content which increased 2.4-fold under high-temperature treatment. The addition of various regulators had different effects: potassium dihydrogen phosphate (KDP) was more protective of yield with heat stress at 7 DAA, while Duntianbao (DTB) had better effects on quality with heat stress at 21 DAA.

Sphingosine-1-phosphate (S1P) is a pleiotropic lysosphingolipid derived from the metabolism of plasma membrane lipids. The interaction between S1P and its ubiquitously expressed G-protein-coupled receptors (S1PR1-5) is crucial in many pathophysiological processes. Emerging evidence suggested a potential role for S1P receptors in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In the present study, we investigated the effects of three different S1P receptors modulators (FTY720, SEW2871 and TY52156) in a recognized rat model of experimental autoimmune vasculitis (EAV). The effects of treatments were evaluated with clinico-pathological parameters including hematuria, proteinuria, crescent formation, pulmonary hemorrhage, etc. In vitro functional studies were performed in a Jurkat T-cell line following stimulations of serum from myeloperoxidase-AAV patients. We found that only the FTY720 treatment significantly alleviated hematuria and proteinuria, and diminished glomerular crescent formation, renal tubulointerstitial lesions and pulmonary hemorrhage in EAV. The attenuation was accompanied by less renal T-cell infiltration, up-regulated mRNA of S1PR1 and down-regulated IL-1β in kidneys, but not altered circulating ANCA levels, suggesting that the therapeutic effects of FTY720 were B-cell independent. Further in vitro studies demonstrated that FTY720 incubation could significantly inhibit the proliferation, adhesion, and migration, and increase apoptosis of T cells. In conclusion, the S1P modulator FTY720 could attenuate EAV through the reduction and inhibition of T cells, which might become a novel treatment of ANCA-associated vasculitis.

Background Antiglomerular basement membrane (anti-GBM) disease is associated with HLA-DRB1*1501 (the major predisposing genetic factor in the disease), with α3127-148 as a nephritogenic T and B cell epitope. Although the cause of disease remains unclear, the association of infections with anti-GBM disease has been long suspected. Methods To investigate whether microbes might activate autoreactive T and B lymphocytes via molecular mimicry in anti-GBM disease, we used bioinformatic tools, including BLAST, SYFPEITHI, and ABCpred, for peptide searching and epitope prediction. We used sera from patients with anti-GBM disease to assess peptides recognized by antibodies, and immunized WKY rats and a humanized mouse model (HLA-DR15 transgenic mice) with each of the peptide candidates to assess pathogenicity. Results On the basis of the critical motif, the bioinformatic approach identified 36 microbial peptides that mimic human α3127-148. Circulating antibodies in sera from patients with anti-GBM recognized nine of them. One peptide, B7, derived from Actinomyces species, induced proteinuria, linear IgG deposition on the GBM, and crescent formation when injected into WKY rats. The antibodies to B7 also targeted human and rat α3127-148. B7 induced T cell activation from human α3127-148-immunized rats. T cell responses to B7 were detected in rats immunized by Actinomyces lysate proteins or recombinant proteins. We confirmed B7's pathogenicity in HLA-DR15 transgenic mice that developed kidney injury similar to that observed in α3135-145-immunized mice. Conclusions Sera from patients with anti-GBM disease recognized microbial peptides identified through a bioinformatic approach, and a peptide from Actinomyces induced experimental anti-GBM GN by T and B cell crossreactivity. These studies demonstrate that anti-GBM disease may be initiated by immunization with a microbial peptide.

Background Gibberellic acid (GA3 ), a plant-growth regulator, is often used to obtain enlarged table grape berries and induce seedlessness in them. However, the effects of GA3 on rachis elongation and bunch compactness have seldom been reported in wine-grape production. We assessed the effects of GA3 spraying on wine-grape inflorescences and bunches and their practical implications for viticulture in the Jiaodong Peninsula, China. Results Various GA3 concentrations were sprayed on field-grown Vitis vinifera L. 'Cabernet Franc' (CF) and 'Cabernet Sauvignon' (CS) grapevines before anthesis in the Jiaodong Peninsula, China, in 2015 and 2016. Inflorescence length during berry development was measured, and flavonoids and aroma compounds in the fruit were detected by high-performance liquid chromatography - mass spectrometry (HPLC-MS) and gas chromatography - mass spectrometry (GC-MS), respectively. For both cultivars, 50 and 100 mg L-1 GA3 caused significant elongation of the rachis, whereas there was no significant effect on inflorescence growth and berry seed number. Anthocyanin, flavonol, and flavan-3-ol levels in mature berries were not significantly influenced by GA3 spraying, whereas C13 -norisoprenoids were modified. Conclusion The application of 50-100 mg L-1 GA3 prior to grapevine anthesis caused elongation of inflorescences and bunches, and eased cluster compactness in CF and CS, and no negative effects were observed on the yield and seed numbers. The concentration and composition of flavonoids and most aroma compounds were not influenced, except that the norisoprenoids were increased by 50 mg L-1 GA3 applications. © 2020 Society of Chemical Industry.

Solid state fermentation with different lignocellulolytic materials as inducers was used for lignocellulolytic enzyme production in this study. Pleurotus ostreatus strains were assessed by measuring laccase, CMCase, and xylanase activities. The secretion potential of the lignocellulolytic enzymes by wild and cultivated strains was analyzed for the first time. The wild and cultivated strain showed their unique capacities for secreting lignocellulolytic enzymes on solid-state fermentation with different lignocellulosic materials. The wild P. ostreatus strain preferred corncob for the secretion of laccase and xylanase activity, but the cultivated strain preferred poplar sawdust. The wild strain and cultivated strain showed a consistent preference for poplar sawdust for the secretion of CMCase activity. The wild strain was advantageous because it achieved the maximum hydrolytic enzyme activities within a short time period. Poplar sawdust and corncob were conducive to laccase secretion by the wild or cultivated strains and the rapid accumulation of laccase on solid-state fermentation. Additionally, continuous, stable laccase production was an extremely important advantage by solid-state fermentation of poplar sawdust, particularly in the wild strain. These findings are helpful in selecting the appropriate strain that corresponds to suitable lignocellulosic materials. The optimization of integrated industrial lignocellulolytic enzyme production can also be achieved.

BACKGROUND: It is a common problem that high‐concentration petroleum hydrocarbon (hc‐PH) is difficult to degrade and remove using biological methods. RESULTS: In this study, when the concentrations of petroleum hydrocarbon (PH) were increased from 972.4 ± 40.3 to 6953.8 ± 294.3 mg L⁻¹, all degradation rates of PH by activated sludge (AS) were beyond 79%. However, the degradation rate of hc‐PH (from 9958.3 ± 401.6 to 19 953.3 ± 896.5 mg L⁻¹) by AS was significantly lower than that of low‐concentration petroleum hydrocarbon (lc‐PH) (from 972.4 ± 40.3 to 6953.8 ± 294.3 mg L⁻¹). Meanwhile, the heterotrophic microorganism number and bacterial community diversity in the hc‐PH environment were lower than those in the lc‐PH environment. Sequencing results of the bacterial community showed that the dominant bacterial community of AS was stable and composed by the genera Pseudomonas, Acinetobacter and Burkholderia‐Paraburkholderia in the hc‐PH condition. Moreover, aimed to enhance the tolerance to hc‐PH stress, the relative abundances of microbial community functions of environmental adaptation, membrane transport, replication and repair were increased. However, the digestive system, circulatory system and endocrine system of the microbial community were significantly disturbed by hc‐PH, which eventually caused the degradation rate of PH by AS to decrease significantly. CONCLUSION: Thus the decrease of microbial community diversity and tolerance ability can be regarded as the main limiting factors to enhance the degradation rate of hc‐PH by microorganisms. © 2019 Society of Chemical Industry

Kinesin-7 CENP-E is an essential kinetochore motor required for chromosome alignment and congression. However, the specific functions of CENP-E in the spermatogenic cells during spermatogenesis remain unknown. In this study, we find that CENP-E proteins are expressed in the spermatogonia, spermatocytes, and the elongating spermatids. CENP-E inhibition by specific inhibitor GSK923295 results in the disruption of spermatogenesis and cell cycle arrest of spermatogenic cells. Both spermatogonia and spermatocytes are arrested in metaphase and several chromosomes are not aligned at the equatorial plate. We find that CENP-E inhibition leads to chromosome misalignment, the spindle disorganization, and the formation of the aneuploidy cells. Furthermore, the inhibition of CENP-E results in the defects in the formation of spermatids, including the sperm head condensation and the sperm tail formation. We have revealed that kinesin-7 CENP-E is essential for chromosome alignment and genome stability of the spermatogenic cells.

Circular RNA (circRNA) is a novel class of noncoding RNAs, and the roles of circRNAs in the development of cardiac hypertrophy remain to be explored. Here, we investigate the potential roles of circRNAs in cardiac hypertrophy. By circRNA sequencing in left ventricular specimens collected from 8-week-old mice with isoproterenol hydrochloride-induced cardiac hypertrophy, we found 401 out of 3323 total circRNAs were dysregulated in the hypertrophic hearts compared with the controls. Of these, 303 circRNAs were upregulated and 98 were downregulated. Moreover, the GO and KEGG analyses revealed that the majority of parental gene of differentially expressed circRNAs were not only related to biological process such as metabolic process and response to stimulus, but also related to pathway such as circulatory system and cardiovascular diseases. On the other hand, total 1974 miRNAs were predicted to binding to these differentially expressed circRNAs, and the possible target mRNAs of those miRNAs were also predicted and analyzed in terms of functional annotation. Finally, we identified that ANF and miR-23a are downstream targets of circRNA wwp1, suggesting that circRNA wwp1 exerts inhibitory roles of cardiac hypertrophy via down-regulation of ANF and miR-23a, which underlying the potential mechanisms whereby circRNA regulates cardiac hypertrophy.

Background: Primary membranous nephropathy (pMN) is less common in women of child-bearing age. The kidney risk factors to adverse maternal-fetal outcomes and the effects of pregnancy on pMN process need to be investigated. Methods: We retrospectively screened all the patients with biopsy-proven pMN from 2008 to 2018. Any cases of pregnancy that occurred at the time of pMN diagnosis or during follow-up were included in the study. Clinical and pathological data were collected from all patients at the time of kidney biopsy and their gestational results were recorded. Results: Of the 27 pregnancies with gestational time of 35.9 ± 4.5 weeks, 10 adverse maternal-fetal events occurred, including fetal loss (11%), preterm delivery (26%), and severe preeclampsia (15%). The kidney parameters were relatively stable with all preserved kidney function. Time-averaged urinary protein (p < 0.001) and serum albumin (p < 0.001), maximum urinary protein (p = 0.001) and minimum serum albumin (p = 0.01) before week 20, anti-phospholipase A2 receptor (PLA2R) positivity (p = 0.03), and no remission during pregnancy (p = 0.004) were risk factors to adverse maternal-fetal outcomes. Time-averaged urinary protein and serum albumin correlated with the birth weight percentile of neonates. Conclusions: Pregnancy in pMN patients showed risks to adverse maternal-fetal events. Heavy proteinuria, especially before week 20 of gestation, severe hypoalbuminemia, positive anti-PLA2R, and no remission were risk factors to worse outcomes.

Objective: Autoantibodies to the α3 chain noncollagen 1 domain of type IV collagen (α3(IV)NC1) are a serological hallmark in the diagnosis of anti-glomerular basement membrane (GBM) disease. The objective of our study was to compare the performance of anti-glomerular basement membrane (GBM) antibody detection by chemiluminescence immunoassay (CIA) and by enzyme-linked immunosorbent assays (ELISAs). Methods: Sera from outpatients who were suspected to have anti-GBM disease and 31 patients with biopsy-proven anti-GBM disease were collected. Thirty normal controls were also included. All samples were tested for anti-GBM antibodies by CIA and commercial ELISA. The anti-GBM antibody-positive samples were confirmed by a homemade ELISA coated with recombinant human α3(IV)NC1. Results: Compared with detection of anti-GBM antibodies with ELISA, detection of anti-GBM antibodies with CIA showed a positivity agreement of 70% and a negativity agreement of 98.6%. Among the 4 patients with different results, the anti-GBM antibody detection by CIA was in agreement with the homemade ELISA coated with recombinant human α3(IV)NC1 and the clinical diagnosis. In 31 patients with anti-GBM disease, good agreement was achieved in the detection of anti-GBM antibodies with CIA, commercial ELISA and the homemade ELISA (100%, 100%). The AUC for CIA and commercial ELISA was 0.987 and 0.966, respectively. Conclusions: The detection of anti-GBM antibodies with CIA demonstrated good sensitivity and specificity and was in good agreement with our homemade ELISA, which seems better than the commercial ELISA in suspected anti-GBM disease patients. The three assays performed in parallel in the diagnosis of anti-GBM disease patients.

Macroautophagy/autophagy, a fundamental process for degradation of macromolecules and organelles, occurs constitutively at a basal level and is upregulated in response to stress. Whether autophagy regulates protein acetylation and microtubule stability in vascular smooth muscle cells (VSMCs) migration, however, remains unknown. Here, we demonstrate that the histone acetyltransferase KAT2A/GCN5 (lysine acetyltransferase 2) binds directly to the autophagosome protein MAP1LC3/LC3 (microtubule associated protein 1 light chain 3) via a conserved LC3-interacting region (LIR) domain. This interaction is required for KAT2A sequestration in autophagosomes and degradation by lysosomal acid hydrolases. Suppression of autophagy results in KAT2A accumulation. KAT2A functions as an acetyltransferase to increase TUBA/α-tubulin acetylation, promote microtubule polymerization and stability, ultimately inhibiting directional cell migration. Our findings indicate that deacetylation of TUBA and perturbation of microtubule stability via selective autophagic degradation of KAT2A are essential for autophagy-promoting VSMC migration. Abbreviations: ACTB: actin beta; ATAT1: alpha tubulin acetyltransferase 1; ATG: autophagy-related; BECN1: beclin 1; CQ: chloroquine; FBS: fetal bovine serum; GST: glutathione S-transferase; H4K16ac: histone H4 lysine 16 acetylation; HASMCs: human aortic smooth muscle cells; HBSS: Hank’s buffered salt solution; HDAC6: histone deacetylase 6; hMOF: human males absent on the first; IP: immunoprecipitation; KAT2A/GCN5: lysine acetyltransferase 2A; Lacta: lactacystin; LIR: LC3-interaction region; MAP1LC3: microtubule associated protein 1 light chain 3; MEFs: mouse embryonic fibroblasts; MTOC: microtubule-organizing center; PE: phosphatidylethanolamine; PtdIns3K: class III phosphatidylinositol 3-kinase; RUNX2: runt-related transcription factor 2; SIRT1: sirtuin 1; SIRT2: sirtuin 2; SQSTM1/p62: sequestosome 1; ULK1: unc-51 like autophagy activating kinase 1; VSMCs: vascular smooth muscle cells; WT: wild-type.

High mobility group box 1 (HMGB1) played pathogenic role in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Recent findings demonstrated that Toll-like receptor 9 (TLR9) was involved in B cell tolerance breaking of autoimmune disease, including AAV. Here, we investigated the effect of HMGB1 on TLR9 in B cells of AAV. In the present work, patients with myeloperoxidase (MPO)-AAV in active stage were recruited. Intracellular TLR9 expression in various B cell subpopulations of the whole blood was detected by flow cytometry and the correlation with clinical data was analysed. Our results showed that intracellular TLR9 expression in B cells, memory B cells and plasmablasts correlated with erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). In particular, TLR9 expression in plasma cells correlated with ESR, CRP, serum creatinine, eGFR, and Birmingham Vasculitis Activity Score. To further explore the effect of HMGB1 on B cell, peripheral blood mononuclear cells (PBMCs) from AAV patients were isolated. After stimulated with HMGB1, TLR9 expression in various B cell subpopulations and proliferation ratio of live B cells were analysed by flow cytometry. We found that TLR9 expression in plasma cells and the proliferation ratio of live B cells by HMGB1 stimulation were significantly upregulated compared with the control group. Therefore, TLR9 expression in plasma cells was associated with disease activity of MPO-AAV. HMGB1 could enhance TLR9 expression in plasma cells and B cell proliferation. These indicated a role of HMGB1 on TLR9 in B cells in MPO-AAV, which would provide potential clues for intervention strategies.

Background C3 glomerulonephritis (C3GN) is a rare disease caused by inherited or acquired complement alternative pathway (CAP) dysregulation, which could also be secondary to monoclonal gammopathy of undetermined significance (MGUS). Herein, we described a patient presenting with C3GN and monoclonal gammopathy, and the pathogenic association between the two diseases was further explored in vitro. Case presentation A 76-year-old Chinese man presented with low serum C3 level, haematuria and nephrotic syndrome, and experienced rapid worsening of renal function over a period of 10 months. His serum and urine immunofixation electrophoresis both revealed a monoclonal IgGλ. A bone marrow puncture showed plasma cell dyscrasias with the highest plasma cell count of 5.25%. Kidney biopsy showed the presence of C3 glomerulonephritis, with exclusive deposits of C3 visible on immunofluorescence, a membranoproliferative pattern on light microscopy and electron dense deposits in sub-epithelial, intramembranous, sub-endothelial and mesangial regions by electron microscopy. The patient was positive for C3 nephritic factor (C3NeF) activity and anti-CFH autoantibodies, and all became negative during disease remission. The anti-CFH autoantibodies purified from the patient’s plasma exchange fluids were proven to be a monoclonal IgGλ, and could inhibit CFH binding to C3b and accelerate the formation of C3 convertase indirectly by interfering with the formation-impeding activity of CFH. No deficiency of candidate genes, especially variants in CFH, was detected in our patient. Based on the pathological and laboratory findings, the diagnosis of monoclonal gammopathy of renal significance (MGRS)-associated C3GN was finally made. Conclusions This is the first demonstration that intact monoclonal immunoglobulin (IgGλ) could act as an anti-CFH antibody and lead to MGRS-associated C3GN by activating the CAP.

Background Both ABO blood group antigens and pathogenic immunoglobulin A1 (IgA1) in patients with IgA nephropathy (IgAN) are influenced by modifications of N-acetylgalactosamine and galactose. The purpose of this study was to assess whether ABO blood type is associated with galactose-deficient IgA1 (Gd-IgA1) in the progression of kidney disease in patients with IgAN. Methods We enrolled 1313 IgAN patients with a median of 44 months follow-up and measured the plasma Gd-IgA1 levels. Multivariate Cox regression models were used to estimate the association between all variables and adverse outcomes. Using the propensity score matching method, 718 IgAN patients with blood type either A or B were selected, and their data were used to assess the association of blood type and Gd-IgA1/serum complement 3 (sC3) with outcomes. Results We found that the risk of adverse outcomes was significantly higher in patients with blood type A than in those with type B (hazard ratio = 1.82, 95% confidence interval 1.23–2.71; P = 0.003) after multivariate adjustment. The Gd-IgA1 levels showed trends similar to the multivariate-adjusted event-free curves for the blood types. However, this higher risk of adverse outcomes in type A than in type B patients was no longer significant after the addition of Gd-IgA1/sC3 to the model. Conclusions IgAN patients with blood type A had a higher risk of adverse outcomes than those with type B, and this risk was associated with Gd-IgA1/sC3. Thus, the ABO blood type may provide a reference for the prognostic factors for individuals with IgAN.

Summary: Impaired interhemispheric connectivity is commonly found in various psychiatric disorders, although how interhemispheric connectivity regulates brain function remains elusive. Here, we use the mouse amygdala, a brain region that is critical for social interaction and fear memory, as a model to demonstrate that contralateral connectivity intensifies the synaptic response of basolateral amygdalae (BLA) and regulates amygdala-dependent behaviors. Retrograde tracing and c-FOS expression indicate that contralateral afferents widely innervate BLA non-randomly and that some BLA neurons innervate both contralateral BLA and the ipsilateral central amygdala (CeA). Our optogenetic and electrophysiological studies further suggest that contralateral BLA input results in the synaptic facilitation of BLA neurons, thereby intensifying the responses to cortical and thalamic stimulations. Finally, pharmacological inhibition and chemogenetic disconnection demonstrate that BLA contralateral facilitation is required for social interaction and memory. Our study suggests that interhemispheric connectivity potentiates the synaptic dynamics of BLA neurons and is critical for the full activation and functionality of amygdalae. : Huang et al. show that contralateral innervation between two basolateral amygdalae (BLA) in the two brain hemispheres evokes the synaptic activity of BLA and intensifies the BLA response to ipsilateral afferents, including cortical and thalamic inputs. BLA contralateral connectivity is required for amygdala-dependent behaviors, including social interaction and memory. Keywords: amygdala, anterior commissure, associative memory, contralateral innervation, social interaction, synaptic facilitation

The newly established virus family Phenuiviridae in Bunyavirales harbors viruses infecting three kingdoms of host organisms (animals, plants, and fungi), which is rare in known virus families. Many phenuiviruses are arboviruses and replicate in two distinct hosts (e.g., insects and humans or rice). Multiple phenuiviruses, such as Dabie bandavirus, Rift Valley fever phlebovirus, and Rice stripe tenuivirus, are highly pathogenic to humans, animals, or plants. They impose heavy global burdens on human health, livestock industry, and agriculture and are research hotspots. In recent years the taxonomy of Phenuiviridae has been expanded greatly, and researches on phenuiviruses have made significant progress. With these advances, this review drew a novel panorama regarding the biomedical significance, distribution, morphology, genomics, taxonomy, evolution, replication, transmission, pathogenesis, and control of phenuiviruses, to aid researchers in various fields to recognize this highly adaptive and very important virus family.

Bermudagrass (Cynodon dactylon Pers.) is a wild Poaceae turfgrass with various genotypes and phenotypes. In this study, 16 wild bermudagrass germplasms were collected from 16 different sites along latitudinal gradients, and different temperature treatments were compiled and used for physiological and transcriptome analysis. To explore the correlation between the key differentially expressed genes and physiological indicators, a total of 14,654 DEGs were integrated from the comparison of different temperature treatments and used for weighted gene co-expression network analysis. Through comparative transcriptome analysis and gene annotation, the results showed that differential gene expression profiles in networks are associated with the plant growth, photosystem, redox system, and transcriptional regulation to cold stress in bermudagrass. In particular, genes encoding HSP70/90 and HsfA3/A8 are not only regulated by temperature stress, but also directly or indirectly interplay with the processes of peroxide scavenging and chlorophyll synthesis under cold stress. Besides, through a weight evaluation analysis of various physiological indexes, we identified an accession of wild bermudagrass with relatively strong cold resistance. These results provide important clues and resources to further study the responses to low-temperature stress in bermudagrass.

Allium victorialis L. (AVL) is a traditional medicinal plant recorded in the Compendium of Materia Medica (the Ming Dynasty). In general, it is used for hemostasis, analgesia, anti-inflammation, antioxidation, and to especially facilitate hepatoprotective effect. In recent years, it has received more and more attention due to its special nutritional and medicinal value. The present study investigates the effect and potential mechanism of AVL against alcoholic liver disease (ALD). C57BL/6 mice were fed Lieber–DeCarli liquid diet containing 5% ethanol plus a single ethanol gavage (5 g/kg), and followed up with the administration of AVL or silymarin. AML12 cells were stimulated with ethanol and incubated with AVL. AVL significantly reduced serum transaminase and triglycerides in the liver and attenuated histopathological changes caused by ethanol. AVL significantly inhibited SREBP1 and its target genes, regulated lipin 1/2, increased PPARα and its target genes, and decreased PPARγ expression caused by ethanol. In addition, AVL significantly enhanced FXR, LXRs, Sirt1, and AMPK expressions compared with the EtOH group. AVL also inhibited inflammatory factors, NLRP3, and F4/80 and MPO, macrophage and neutrophil markers. In vitro, AVL significantly reduced lipid droplets, lipid metabolism enzymes, and inflammatory factors depending on FXR activation. AVL could ameliorate alcoholic steatohepatitis, lipid deposition and inflammation in ALD by targeting FXR activation.

Mitochondria are essential organelles for cellular energy production, metabolic homeostasis, calcium homeostasis, cell proliferation, and apoptosis. About 99% of mammalian mitochondrial proteins are encoded by the nuclear genome, synthesized as precursors in the cytosol, and imported into mitochondria by mitochondrial protein import machinery. Mitochondrial protein import systems function not only as independent units for protein translocation, but also are deeply integrated into a functional network of mitochondrial bioenergetics, protein quality control, mitochondrial dynamics and morphology, and interaction with other organelles. Mitochondrial protein import deficiency is linked to various diseases, including cardiovascular disease. In this review, we describe an emerging class of protein or genetic variations of components of the mitochondrial import machinery involved in heart disease. The major protein import pathways, including the presequence pathway (TIM23 pathway), the carrier pathway (TIM22 pathway), and the mitochondrial intermembrane space import and assembly machinery, related translocases, proteinases, and chaperones, are discussed here. This review highlights the importance of mitochondrial import machinery in heart disease, which deserves considerable attention, and further studies are urgently needed. Ultimately, this knowledge may be critical for the development of therapeutic strategies in heart disease.

Stenotrophomonas maltophilia has been reported in various ocular infections, including keratitis, conjunctivitis, preseptal cellulitis, and endophthalmitis, all of which may lead to vision loss. However, the S. maltophilia strain is resistant to a wide variety of antibiotics, including penicillins, third-generation cephalosporins, aminoglycosides, and imipenem. In this study, we retrospectively reviewed the clinical characteristics, antibiotic susceptibility, antimicrobial minimum inhibitory concentrations (MICs), and visual outcomes for S. maltophilia endophthalmitis. The data of 9 patients with positive S. maltophilia cultures in a tertiary referral center from 2010 to 2019 were reviewed. Cataract surgery (n = 8, 89%) was the most common etiology, followed by intravitreal injection (n = 1, 11%). S. maltophilia’s susceptibility to levofloxacin and moxifloxacin was observed in 6 cases (67%). Seven isolates were resistant to sulfamethoxazole-trimethoprim (78%). The MIC90 for S. maltophilia was 256, 256, 256, 8, 12, 12, 12, and 8 μg/mL for amikacin, cefuroxime, ceftazidime, tigecycline, sulfamethoxazole-trimethoprim, levofloxacin, galtifloxacin, and moxifloxacin, respectively. Final visual acuity was 20/200 or better in 5 patients (56%). Fluoroquinolones and tigecycline exhibited low antibiotic MIC90. Therefore, the results suggest that fluoroquinolones can be used as first-line antibiotics for S. maltophilia endophthalmitis.

Background: The roots of Panax species are widely used in the East because of their high medicinal and economic value. They are similar in plant morphology and chemical composition, but have quite differences in medicinal properties and efficacy, therefore, genetic diversity and variety identification of Panax species is particularly important. Methods: We screened 7 Simple Sequence Repeat (SSR) markers from expressed sequence tags (ESTs) database of Panax species in NCBI. Using these markers test SSR polymorphism in Panax species. Results: Seven SSR markers could successfully identify Panax ginseng, Panax quinquefolium, Panax notoginseng, and their commercial products. Among three ginseng varieties, garden ginseng, forest ginseng, and wild ginseng, the polymorphism of EST-SSR markers decreased gradually, which may be related to age and environment. Two pairs of EST-SSR primers can specifically identify three ginseng cultivars. The phylogenetic relationships analysis showed that Panax ginseng and Panax quinquefolium were closer than Panax notoginseng. Compared with wild ginseng, the relationship between the garden ginseng and the forest ginseng was closer. Conclusion: SSR molecular markers have high repeatability and can be used as reliable molecular markers for genetic diversity and variety identification of Panax species.

The heart is a high energy demand organ and enhancing mitochondrial function is proposed as the next-generation therapeutics for heart failure. Our previous study found that anthelmintic drug niclosamide enhanced mitochondrial respiration and increased adenosine triphosphate (ATP) production in cardiomyocytes, therefore, this study aimed to determine the effect of niclosamide on heart failure in mice and the potential molecular mechanisms. The heart failure model was induced by transverse aortic constriction (TAC) in mice. Oral administration of niclosamide improved TAC-induced cardiac hypertrophy, cardiac fibrosis, and cardiac dysfunction in mice. Oral administration of niclosamide reduced TAC-induced increase of serum IL-6 in heart failure mice. In vitro, niclosamide within 0.1 μM increased mitochondrial respiration and ATP production in mice heart tissues. At the concentrations more than 0.1 μM, niclosamide reduced the increased interleukin- 6 (IL-6) mRNA expression in lipopolysaccharide (LPS)-stimulated RAW264.7 and THP-1 derived macrophages. In cultured primary cardiomyocytes and cardiac fibroblasts, niclosamide (more than 0.1 μM) suppressed IL-6- and phenylephrine-induced cardiomyocyte hypertrophy, and inhibited collagen secretion from cardiac fibroblasts. In conclusion, niclosamide attenuates heart failure in mice and the underlying mechanisms include enhancing mitochondrial respiration of cardiomyocytes, inhibiting collagen secretion from cardiac fibroblasts, and reducing the elevated serum inflammatory mediator IL-6. The present study suggests that niclosamide might be therapeutic for heart failure.

Apolipoprotein E (ApoE), an essential plasma apolipoprotein, has three isoforms (E2, E3, and E4) in humans. E2 is associated with type III hyperlipoproteinemia. E4 is the major susceptibility gene to Alzheimer’s disease (AD) and coronary heart disease (CHD). We investigated lipid metabolism and atherosclerotic lesions of novel humanized ApoE knockin (hApoE KI) rats in comparison to wide-type (WT) and ApoE knockout (ApoE KO) rats. The hApoE2 rats showed the lowest bodyweight and white fat mass. hApoE2 rats developed higher serum total cholesterol (TC), total triglyceride (TG), and low- and very low density lipoprotein (LDL-C&amp, VLDL-C). ApoE KO rats also exhibited elevated TC and LDL-C&amp, VLDL-C. Only mild atherosclerotic lesions were detected in hApoE2 and ApoE KO aortic roots. Half of the hApoE2 rats developed hepatic nodular cirrhosis. A short period of the Paigen diet (PD) treatment led to the premature death of the hApoE2 and ApoE KO rats. Severe vascular wall thickening of the coronary and pulmonary arteries was observed in 4-month PD-treated hApoE4 rats. In conclusion, hApoE2 rats develop spontaneous hyperlipidemia and might be suitable for studies of lipid metabolism-related diseases. With the PD challenge, hApoE4 KI rats could be a novel model for the analysis of vascular remodeling.

This material is based on work supported by the National Science Foundation under grant no. 1845586. The work of T.T.K.H. was supported by grant no. 501.01-2016.02 from the Vietnam National Foundation for Science and Technology Development (NAFOSTED). A.O. was supported by the Ministry of Science and Higher Education (grant no. 626/STYP/12/2017). A.S. and P.S. were supported by National Science Center-Poland (grant no. 2014/13/B/HS6/02644). Marina Butovskaya and D.D. were supported by State assignment project No. 01201370995 of the Institute of Ethnology and Anthropology, Moscow, Russia. P.G., A.L. and N.M. were supported by the Hungarian Scientific Research Fund-(OTKA; grant no. K125437). F.J. was supported by the National Nature Science Foundation of China (grant no. 71971225). G.A. was supported by UKRI/GCRF Gender, Justice, Security Grant (grant no. AH/S004025/1)., A wide range of literature connects sex ratio and mating behaviours in non-human animals. However, research examining sex ratio and human mating is limited in scope. Prior work has examined the relationship between sex ratio and desire for short-term, uncommitted mating as well as outcomes such as marriage and divorce rates. Less empirical attention has been directed towards the relationship between sex ratio and mate preferences, despite the importance of mate preferences in the human mating literature. To address this gap, we examined sex ratio’s relationship to the variation in preferences for attractiveness, resources, kindness, intelligence and health in a long-term mate across 45 countries (n = 14 487). We predicted that mate preferences would vary according to relative power of choice on the mating market, with increased power derived from having relatively few competitors and numerous potential mates. We found that each sex tended to report more demanding preferences for attractiveness and resources where the opposite sex was abundant, compared to where the opposite sex was scarce. This pattern dovetails with those found for mating strategies in humans and mate preferences across species, highlighting the importance of sex ratio for understanding variation in human mate preferences., National Science Foundation (NSF) 1845586, National Foundation for Science & Technology Development (NAFOSTED) 501.01-2016.02, Ministry of Science and Higher Education, Poland, European Commission 626/STYP/12/2017, National Science Centre, Poland 2014/13/B/HS6/02644, Institute of Ethnology and Anthropology, Moscow, Russia 01201370995, Orszagos Tudomanyos Kutatasi Alapprogramok (OTKA) K125437, National Natural Science Foundation of China (NSFC) 71971225, UKRI/GCRF Gender, Justice, Security Grant AH/S004025/1

Lysine-specific demethylase 5A (KDM5A, also named RBP2 or JARID1A) is a demethylase that can remove methyl groups from histones H3K4me1/2/3. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, drug resistance, and is associated with poor prognosis. Pharmacological inhibition of KDM5A has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of KDM5A, its role in carcinogenesis, a comparison of currently available approaches for screening KDM5A inhibitors, a classification of KDM5A inhibitors, and its potential as a drug target in cancer therapy.

Background and aims: Studies of hereditary transthyretin amyloidosis (ATTRv amyloidosis) in South-East Asia are underrepresented in the literature. We report the unique phenotypic and genetic characteristics of this disorder in a multiracial South-East Asian cohort. Methods: Patients with genetically proven ATTRv amyloidosis were identified over a 13-year period (2007–2020) at the National Neuroscience Institute, Singapore. Clinical, laboratory, genotypic and electrophysiological features were retrospectively reviewed. Results: 29 patients comprising Chinese, Malay, Burmese, Vietnamese and Indonesians with ATTRv amyloidosis were identified. Somatic neuropathy was the most common initial presentation, followed by carpal tunnel syndrome, autonomic dysfunction and cardiac dysfunction. ATTR-A97S (p.Ala117Ser) was the most common variant found in 14 patients, constituting 66.7%of ethnic Chinese patients and 48.3%of the entire cohort. Five patients had early-onset disease (age

Oncogenic KRAS mutations combined with the loss of the LKB1 tumor-suppressor gene (KL) are strongly associated with aggressive forms of lung cancer. N6-methyladenosine (m6A) in mRNA is a crucial epigenetic modification that controls cancer self-renewal and progression. However, the regulation and role of m6A modification in this cancer are unclear. We found that decreased m6A levels correlated with the disease progression and poor survival for KL patients. The correlation was mediated by a special increase in ALKBH5 (AlkB family member 5) levels, an m6A demethylase. ALKBH5 gain- or loss-of function could effectively reverse LKB1 regulated cell proliferation, colony formation, and migration of KRAS-mutated lung cancer cells. Mechanistically, LKB1 loss upregulated ALKBH5 expression by DNA hypermethylation of the CTCF-binding motif on the ALKBH5 promoter, which inhibited CTCF binding but enhanced histone modifications, including H3K4me3, H3K9ac, and H3K27ac. This effect could successfully be rescued by LKB1 expression. ALKBH5 demethylation of m6A stabilized oncogenic drivers, such as SOX2, SMAD7, and MYC, through a pathway dependent on YTHDF2, an m6A reader protein. The above findings were confirmed in clinical KRAS-mutated lung cancer patients. We conclude that loss of LKB1 promotes ALKBH5 transcription by a DNA methylation mechanism, reduces m6A modification, and increases the stability of m6A target oncogenes, thus contributing to aggressive phenotypes of KRAS-mutated lung cancer.

Terpios hoshinota is an aggressive, space-competing sponge that kills various stony corals. Outbreaks of this species have led to intense damage to coral reefs in many locations. Here, the first large-scale 16S rRNA gene survey across three oceans revealed that bacteria related to the taxa Prochloron, Endozoicomonas, SAR116, Ruegeria, and unclassified Proteobacteria were prevalent in T. hoshinota. A Prochloron-related bacterium was the most dominant and prevalent cyanobacterium in T. hoshinota. The complete genome of this uncultivated cyanobacterium and pigment analysis demonstrated that it has phycobiliproteins and lacks chlorophyll b, which is inconsistent with the definition of Prochloron. Furthermore, the cyanobacterium was phylogenetically distinct from Prochloron, strongly suggesting that it should be a sister taxon to Prochloron. Therefore, we proposed this symbiotic cyanobacterium as a novel species under the new genus Candidatus Paraprochloron terpiosi. Comparative genomic analyses revealed that 'Paraprochloron' and Prochloron exhibit distinct genomic features and DNA replication machinery. We also characterized the metabolic potentials of 'Paraprochloron terpiosi' in carbon and nitrogen cycling and propose a model for interactions between it and T. hoshinota. This study builds a foundation for the study of the T. hoshinota microbiome and paves the way for better understanding of ecosystems involving this coral-killing sponge.