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To compare the effects of aminosalicylic acid, glucocorticoids and immunosuppressants on the expression levels of multidrug resistance genes in patients with ulcerative colitis (UC), with the aim of providing a theoretical and therapeutic basis for the diagnosis, treatment, and prevention of UC. Fresh colonic mucosal tissues or postoperative pathological biopsies from 148 UC patients were collected, and the distribution sites and morphology of P-glycoprotein (P-gp) were detected using immunohistochemical staining. RT-PCR was used to quantify the expression levels of multidrug resistance gene (MDR1) mRNA before and after the corresponding treatment, and the effects of aminosalicylic acid, glucocorticoids and immunosuppressive drugs on P-gp were compared. In addition, the effects of the three drugs on MDR1 mRNA were analyzed. Administration of 5-aminosalicylic acid (5-ASA) drugs did not correlate with MDR1 expression in UC, whereas administration of glucocorticoids and immunosuppressive drugs was positively correlated with MDR1 expression profile. The expression levels of MDR1 mRNA and its product P-gp were significantly upregulated in patients who did not respond to glucocorticoids and immunosuppressive drugs. 5-ASA had no effect on the expression levels of MDR1 and its product P-gp in patients with a confirmed diagnosis of UC. However, the use of glucocorticoids and immunosuppressants can increase the expression level of MDR1., (© 2022. The Author(s).)

Background: Polypodiales suborder Dennstaedtiineae contain a single family Dennstaedtiaceae, eleven genera, and about 270 species, and include some groups that were previously placed in Dennstaedtiaceae, Hypolepidaceae, Monachosoraceae, and Pteridaceae. The classification and phylogenetic relationships among these eleven genera have been poorly understood. To explore the deep relationships within suborder Dennstaedtiineae and estimate the early diversification of this morphologically heterogeneous group, we analyzed complete plastomes of 57 samples representing all eleven genera of suborder Dennstaedtiineae using maximum likelihood and Bayesian inference., Results: The phylogenetic relationships of all the lineages in the bracken fern family Dennstaedtiaceae were well resolved with strong support values. All six genera of Hypolepidoideae were recovered as forming a monophyletic group with full support, and Pteridium was fully supported as sister to all the other genera in Hypolepidoideae. Dennstaedtioideae (Dennstaedtia s.l.) fell into four clades with full support: the Microlepia clade, the northern Dennstaedtia clade, the Dennstaedtia globulifera clade, and the Dennstaedtia s.s. clade. Monachosorum was strongly resolved as sister to all the remaining genera of suborder Dennstaedtiineae. Based on the well resolved relationships among genera, the divergence between Monachosorum and other groups of suborder Dennstaedtiineae was estimated to have occurred in the Early Cretaceous, and all extant genera (and clades) in Dennstaedtiineae, were inferred to have diversified since the Late Oligocene., Conclusion: This study supports reinstating a previously published family Monachosoraceae as a segregate from Dennstaedtiaceae, based on unique morphological evidence, the shady habitat, and the deep evolutionary divergence from its closest relatives., (© 2022. The Author(s).)

Background: Lactate has long been considered an intermediate by-product of glucose metabolism. However, in recent years, accumulating evidence reveals that lactate has unique biological activities. In previous studies, lactate signaling was shown to inhibit inflammation. Furthermore, in vitro experiments have shown that lactate can promote the transformation of pro-inflammatory macrophages into anti-inflammatory macrophages. However, no in vivo studies have shown whether lactate can alleviate inflammation., Methods: RAW 264.7 macrophages were stimulated by LPS to induce an M1 phenotype, and cultured with low and high concentrations of lactate. The cells were then observed for phenotypic transformations and expression of inflammatory mediators and surface markers. The expression of inflammatory factors was also analyzed in the cell-free supernatant fraction. Further, a mouse model of DSS-induced colitis was established and treated with lactate. Colonic tissue injury was monitored by histopathological examinations., Results: The in vitro experiments showed that lactate promoted the transformation of activated macrophages to M2 phenotype and decreased the expression of TLR4-mediated NF-κB signaling proteins and inflammatory factors. In the DSS-induced colitis mouse model, lactate promoted the phenotypic transformation of macrophages in colonic tissue, reduced inflammation and organ damage, inhibited the activation of TLR4/NF-κB signaling pathway, decreased the serum levels of pro-inflammatory factors, increased the expression of anti-inflammatory factors, promoted the repair of the intestinal mucosal barrier and reduced the severity of colitis., Conclusions: Lactate inhibits the TLR/NF-κB signaling pathway and the production of pro-inflammatory factors by promoting polarization of macrophages. In addition, lactate promotesthe repair of the intestinal mucosal barrier and protects intestinal tissue in inflammation. Furthermore, lactate is relatively safe. Therefore, lactate is a promising and effective drug for treating inflammation through immunometabolism regulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Yu, Yan, Liang, Ma, Long, Du, Mao and Liu.)

Infection with helminths can modulate the host immune response, which ultimately shape morbidity and mortality of the associated diseases. We studied key cytokines for essential immune response in sera from 229 southeastern China individuals infected with Clonorchis sinensis and 60 individuals without C. sinensis infection, and measured serum specific IgG and IgE against worms in these people. Individuals infected with C. sinensis had significantly higher antigen-specific IgG and IgE levels, which were positively correlated with egg counts in feces. However, less enhancement of IgE antibody was observed in females when compared to males with similar infection levels. C. sinensis infection caused diminished Th1 cytokines (IL-1β, IL-2, IL-12p70, IFN-γ and TNF-α), Th2 cytokine (IL-4), as well as Th17 cytokine (IL-17A) in sera, which showed decreasing trend by infection intensity. Notably, these phenotypes were more significant in females than those in males. Although C. sinensis infection is associated with the development of hepatobiliary diseases, there was no significant correlation between the dampened cytokine profiles and the hepatobiliary morbidities. Our study indicates C. sinensis infection is strongly related to the immune suppression in human. Sex differences shape the immune milieus of clonorchiasis. This study provides a better understanding of how worms affect immune responses and cause a long-term immune alternation in humans with C. sinensis infection., Competing Interests: The authors have declared that no competing interests exist.

The pollution source identification methods based on traditional water quality monitoring and pollutant discharge loading typically require a high frequency of monitoring and generate a level of uncertainty in the identification results, owing to their limitations on the accurate and quantitative assessment of pollution source identification, migration, and transformation. This study combined multivariate statistical analysis and stable isotope technology to identify groundwater pollution sources in a typical multiple land-use area of the Chengdu Plain. A positive matrix factorization (PMF) model was adopted to reduce the interference of mass environmental factors on source identification and to determine the main factors influencing groundwater quality. Subsequently, a Bayesian stable isotope mixing model was developed to quantify the apportionment of each pollution source to groundwater nitrate (NO 3 - ) with the consideration of hydro-chemical and land-use information. The results showed that the concentrations of NO 3 - , NO 2 - , NH 4 + , Mn, Fe, SO 4 2- , and Cl - in groundwater of the study area exceeded the standard to different extents, presenting spatial variation. The main form of inorganic nitrogen in groundwater was NO 3 - . In general, concentrations of groundwater NO 3 - were the highest in vegetable fields (9.29 mg·L -1 on average), followed by livestock and poultry breeding farms (7.66 mg·L -1 ) and arable land (7.09 mg·L -1 ), whereas concentrations of groundwater NO 3 - in industrial areas were the lowest (2.20 mg·L -1 ). Groundwater quality in the study area was affected by geological processes, agricultural activities, hydrogeochemical evolution, and domestic and industrial discharges. Agricultural activities were the main contributor to the increase in groundwater NO 3 - in the study area. Chemical fertilizer (32%) and soil nitrogen (25%) contributed greatly to groundwater NO 3 - in agricultural areas, whereas sewage (28%) and atmospheric precipitation (27%) contributed most groundwater NO 3 - in industrial areas. Thus, the combination of multivariate statistical analysis and stable isotope technology could identify groundwater pollution sources and their apportionment effectively, providing scientific support for the prevention and control of groundwater pollution.

The combined use of two or more different drugs can better promote nerve recovery and its prognosis for treatment of stroke. Salvianolate lyophilized injection (SLI) made from the aqueous extraction of salvia miltiorrhiza and Xueshuantong injection (lyophilized) (XST) made from the Panax Notoginseng extraction are two herbal standardized preparations that have been widely used in China for the treatment of ischemic stroke. In this study, we investigated the neuroprotective effects of XST combined with SLI in the recovery stage of middle cerebral artery occlusion / reperfusion (MCAO/R) injury rat. Wistar rats were subjects to MCAO/R, then were treated with SLI or XST alone, or with their combination (1X1S) via tail injection daily for 14 days. The pathological status of the brain was detected by neurological deficit scores, TTC, regional cerebral blood flow and Nissl staining. Golgi-Cox staining was used to assess dendritic, axonal and synaptic remodeling. The expression of MAP-2, β-Tubulin, PSD95, SYN, BDNF and VEGF were analyzed by western blotting and immunofluorescence. The results showed that administration of 1X1S not only significantly decreased neurological scores and infarct volumes, but also increased regional cerebral blood flow, strengthened dendritic and synaptic remodeling compared with XST, SLI used alone. And the mechanism of combined of 1X1S to exert neuroprotection may be associated with PI3K/ AKT/ mTOR and RhoA/ROCK2 pathways. Overall, these findings suggest that combination of XST and SLI promotes dendritic spine density and synaptic plasticity via upregulation of the PI3K/ AKT/ mTOR pathways and inhabitation the RhoA/ROCK2 signaling pathway in rat with MCAO/R, showing its multiple-action-multiple-target efficacy and suggest a potential new strategy for ischemia., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely used in the treatment of hypertension. Hypertension is often accompanied by osteoporosis. However, the relationship between ACEI/ARB and fractures remains controversial. The purpose of this meta-analysis was to update the potential relationship between ACEI/ARB and fractures., Methods: This meta-analysis was identified through PubMed, EMBASE, Cochrane Library, and Web of Science. Related studies about ACEI/ARB with the risk of fracture were published from inception to June 2022., Results: Nine qualified prospective designed studies, involving 3,649,785 subjects, were included in this analysis. Overall, the RRs of ACEI compared with the nonusers were 0.98 (95% CI: 0.88, 1.10; P < 0.001) for composite fractures and 0.96 (95% CI: 0.87, 1.05; P =0.048) for hip fractures; the RRs of ARB compared to the nonusers were 0.82 (95% CI: 0.73, 0.91; P < 0.001) for composite fractures and 0.85 (95% CI: 0.74, 0.97; P =0.028) for hip fractures. Furthermore, in the subgroup analysis, male may benefit from ARB (RR = 0.65, 95% CI: 0.49, 0.89, P =0.028), and the European may also benefit from ARB (RR = 0.86, 95% CI: 0.80, 0.93, P =0.015)., Conclusions: ACEI usage will not decrease the risk of osteoporosis fracture. On the contrary, ARB usage can decrease the risk of total fracture and hip fracture, especially for males and Europeans. Compared with ACEI, for patients at higher risk of fracture in cardiovascular diseases such as hypertension, the protective effect of ARB should be considered., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Jing Wu et al.)

Background: The study aims to evaluate the accuracy of the generative adversarial networks (GAN) for reconstructing bony midfacial defects., Methods: According to anatomy, the bony midface was divided into five subunit structural regions and artificial defects are manually created on the corresponding CT images. GAN is trained to reconstruct artificial defects to their previous normal shape and tested. The clinical defects are reconstructed by the trained GAN, where the midspan defects were used for qualitative evaluation and the unilateral defects were used for quantitative evaluation. The cosine similarity and the mean error are used to evaluate the accuracy of reconstruction. The Mann-Whitney U test is used to detect whether reconstruction errors were consistent in artificial and unilateral clinical defects., Results: This study included 518 normal CT data, with 415 in training set and 103 in testing set, and 17 real patient data, with 2 midspan defects and 15 unilateral defects. Reconstruction of midspan clinical defects assessed by experts is acceptable. The cosine similarity in the reconstruction of artificial defects and unilateral clinical defects is 0.97 ± 0.01 and 0.96 ± 0.01, P = 0.695. The mean error in the reconstruction of artificial defects and unilateral clinical defects is 0.59 ± 0.31 mm and 0.48 ± 0.08 mm, P = 0.09., Conclusion: GAN-based virtual reconstruction technology has reached a high accuracy in testing set, and statistical tests suggest that it can achieve similar results in real patient data. This study has preliminarily solved the problem of bony midfacial defect without reference., (© 2022. The Author(s).)

Wintergreen oil is a folk medicine widely used in foods, pesticides, cosmetics and drugs. In China, nine out of 47 species within Gaultheria (Ericaceae) are traditionally used as Chinese medicinal wintergreens; however, phylogenetic approaches currently used to discriminating these species remain unsatisfactory. In this study, we sequenced and characterized plastomes from nine Chinese wintergreen species and identified candidate DNA barcoding regions for Gaultheria . Each Gaultheria plastome contained 110 unique genes (76 protein-coding, 30 tRNA, and four rRNA genes). Duplication of trnfM , rps14 , and rpl23 genes were detected, while all plastomes lacked ycf1 and ycf2 genes. Gaultheria plastomes shared substantially contracted SSC regions that contained only the ndhF gene. Moreover, plastomes of Gaultheria leucocarpa var. yunnanensis contained an inversion in the LSC region and an IR expansion to cover the ndhF gene. Multiple rearrangement events apparently occurred between the Gaultheria plastomes and those from several previously reported families in Ericales. Our phylogenetic reconstruction using 42 plastomes revealed well-supported relationships within all nine Gaultheria species. Additionally, seven mutational hotspot regions were identified as potential DNA barcodes for Chinese medicinal wintergreens. Our study is the first to generate complete plastomes and describe the structural variations of the complicated genus Gaultheria. In addition, our findings provide important resources for identification of Chinese medicinal wintergreens., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Kunming Institute of Botany, Chinese Academy of Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

The aim of this study was to investigate the occurrence and molecular characteristics of Bartonella infections in small rodents in the Shangdang Basin, China. Small rodents were captured using snap traps, and their liver, spleen, and kidney tissues were harvested for Bartonella detection and identification using a combination of real-time PCR of the ssrA gene (296 bp) and conventional PCR and sequencing of the gltA gene (379 bp). Results showed that 55 of 147 small rodents to be positive for Bartonella, with a positivity rate of 37.41%, and 95% confidence interval of 29.50%- 45.33%. While the positivity rate across genders (42.62% in males and 33.72% in females, χ2 = 1.208, P = 0.272) and tissues (28.57% in liver, 33.59% in spleen, and 36.76% in kidney, χ2 = 2.197, P = 0.333) of small rodents was not statistically different, that in different habitats (5.13% in villages, 84.44% in forests, and 54.17% in farmlands, χ2 = 80.105, P<0.001) was statistically different. There were 42 Bartonella sequences identified in six species, including 30 B. grahamii, three B. phoceensis, two B. japonica, two B. queenslandensis, one B. fuyuanensis and four unknown Bartonella species from Niviventer confucianus, Apodemus agrarius and Tscherskia triton. In addition to habitat, Bartonella species infection could be affected by the rodent species as well. Among the Bartonella species detected in this area, B. grahamii was the dominant epidemic species (accounting for 71.43%). B. grahamii exhibited four distinct clusters, and showed a certain host specificity. In addition, 11 haplotypes of B. grahamii were observed using DNASP 6.12.03, among which nine haplotypes were novel. Overall, high occurrence and genetic diversity of Bartonella were observed among small rodents in the Shangdang Basin; this information could potentially help the prevention and control of rodent-Bartonella species in this area., Competing Interests: The authors have declared that no competing interests exist.

Structural variation of plastid genomes (plastomes), particularly large inversions and gene losses, can provide key evidence for the deep phylogeny of plants. In this study, we investigated the structural variation of fern plastomes in a phylogenetic context. A total of 127 plastomes representing all 50 recognized families and 11 orders of ferns were sampled, making it the most comprehensive plastomic analysis of fern lineages to date. The samples included 42 novel plastomes of 15 families with a focus on Hymenophyllales and Gleicheniales. We reconstructed a well-supported phylogeny of all extant fern families, detected significant structural synapomorphies, including 9 large inversions, 7 invert repeat region (IR) boundary shifts, 10 protein-coding gene losses, 7 tRNA gene losses or anticodon changes, and 19 codon indels (insertions or deletions) across the deep phylogeny of ferns, particularly on the backbone nodes. The newly identified inversion V5, together with the newly inferred expansion of the IR boundary R5, can be identified as a synapomorphy of a clade composed of Dipteridaceae, Matoniaceae, Schizaeales, and the core leptosporangiates, while a unique inversion V4, together with an expansion of the IR boundary R4, was verified as a synapomorphy of Gleicheniaceae. This structural evidence is in support of our phylogenetic inference, thus providing key insight into the paraphyly of Gleicheniales. The inversions of V5 and V7 together filled the crucial gap regarding how the "reversed" gene orientation in the IR region characterized by most extant ferns (Schizaeales and the core leptosporangiates) evolved from the inferred ancestral type as retained in Equisetales and Osmundales. The tRNA genes trnR-ACG and trnM-CAU were assumed to be relicts of the early-divergent fern lineages but intact in most Polypodiales, particularly in eupolypods; and the loss of the tRNA genes trnR-CCG, trnV-UAC , and trnR-UCU in fern plastomes was much more prevalent than previously thought. We also identified several codon indels in protein-coding genes within the core leptosporangiates, which may be identified as synapomorphies of specific families or higher ranks. This study provides an empirical case of integrating structural and sequence information of plastomes to resolve deep phylogeny of plants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Du, Kuo, Zuo, Li and Lu.)

Aim: Clinical utility of doxorubicin (DOX) is limited by its cardiotoxic side effect, and the underlying mechanism still needs to be fully elucidated. This research aimed to examine the role of (pro)renin receptor (PRR) in DOX-induced heart failure (HF) and its underlying mechanism., Main Methods: Sprague Dawley (SD) rats were injected with an accumulative dosage of DOX (15 mg/kg) to induce HF. Cardiac functions were detected by transthoracic echocardiography examination. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK) in serum were detected, and oxidative stress related injuries were evaluated. Furthermore, the mRNA expression of PRR gene and its related genes were detected by real-time PCR (RT-PCR), and protein levels of PRR, RAC1, NOX4 and NOX2 were determined by Western blot. Reactive oxygen species (ROS) were determined in DOX-treated rats or cells. Additionally, PRR and RAC1 were silenced with their respective siRNAs to validate the in vitro impacts of PRR/RAC1 on DOX-induced cardiotoxicity. Moreover, inhibitors of PRR and RAC1 were used to validate their effects in vivo ., Key Findings: PRR and RAC1 expressions increased in DOX-induced HF. The levels of CK and LDH as well as oxidative stress indicators increased significantly after DOX treatment. Oxidative injury and apoptosis of cardiomyocytes were attenuated both in vivo and in vitro upon suppression of PRR or RAC1. Furthermore, the inhibition of PRR could significantly down-regulate the expressions of RAC1 and NOX4 but not that of NOX2, while the inhibition of RAC1 did not affect PRR., Significance: Our findings showed that PRR inhibition could weaken RAC1-NOX4 pathway and alleviate DOX-induced HF via decreasing ROS production, thereby suggesting a promising target for the treatment of DOX-induced HF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Du, Xiang, Gao, Peng and Liu.)

Background: Members of the genus Novius Mulsant, 1846 (= Rodolia Mulsant, 1850) (Coleoptera, Coccinellidae), play important roles in the biological control of cotton cushion scale pests, especially those belonging to Icerya. Since the best-known species, the vedalia beetle Novius cardinalis (Mulsant, 1850) was introduced into California from Australia, more than a century of successful use in classical biological control, some species of Novius have begun to exhibit some field adaptations to novel but related prey species. Despite their economic importance, relatively little is known about the underlying genetic adaptations associated with their feeding habits. Knowledge of the genome sequence of Novius is a major step towards further understanding its biology and potential applications in pest control., Results: We report the first high-quality genome sequence for Novius pumilus (Weise, 1892), a representative specialist of Novius. Computational Analysis of gene Family Evolution (CAFE) analysis showed that several orthogroups encoding chemosensors, digestive, and immunity-related enzymes were significantly expanded (P < 0.05) in N. pumilus compared to the published genomes of other four ladybirds. Furthermore, some of these orthogroups were under significant positive selection pressure (P < 0.05). Notably, transcriptome profiling demonstrated that many genes among the significantly expanded and positively selected orthogroups, as well as genes related to detoxification were differentially expressed, when N. pumilus feeding on the nature prey Icerya compared with the no feeding set. We speculate that these genes are vital in the Icerya adaptation of Novius species., Conclusions: We report the first Novius genome thus far. In addition, we provide comprehensive transcriptomic resources for N. pumilus. The results from this study may be helpful for understanding the association of the evolution of genes related to chemosensing, digestion, detoxification and immunity with the prey adaptation of insect predators. This will provide a reference for future research and utilization of Novius in biological control programs. Moreover, understanding the possible molecular mechanisms of prey adaptation also inform mass rearing of N. pumilus and other Novius, which may benefit pest control., (© 2022. The Author(s).)

While roses are today among the most popular ornamental plants, the petals and fruits of some cultivars have flavored foods for millennia. The genetic origins of these edible cultivars remain poorly investigated. We collected the major varieties of edible roses available in China, assembled their plastome sequences, and phased the haplotypes for internal transcribed spacers (ITS1/ITS2) of the 18S-5.8S-26S nuclear ribosomal cistron. Our phylogenetic reconstruction using 88 plastid genomes, of primarily maternal origin, uncovered well-supported genetic relationships within Rosa, including all sections and all subgenera. We phased the ITS sequences to identify potential donor species ancestral to the development of known edible cultivars. The tri-parental Middle-Eastern origin of R. × damascena, the species most widely used in perfume products and food additives, was confirmed as a descendent of past hybridizations among R. moschata, R. gallica, and R. majalis/R. fedtschenkoana/R. davurica. In contrast, R. chinensis, R. rugosa, and R. gallica, in association with six other wild species, were the main donors for fifteen varieties of edible roses. The domesticated R. rugosa 'Plena' was shown to be a hybrid between R. rugosa and R. davurica, sharing a common origin with R. 'Fenghua'. Only R. 'Jinbian' and R. 'Crimson Glory' featured continuous flowering. All remaining cultivars of edible roses bloomed only once a year. Our study provides important resources for clarifying the origin of edible roses and suggests a future for breeding new cultivars with unique traits, such as continuous flowering., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Objective: The aim of this study was to analyze the epidemiological characteristics of mortality in the emergency department of Beijing Tongren Hospital from 2014 to 2019., Methods: A total of 781 cases in the hospital's emergency department that resulted in mortality were retrospectively screened, and epidemiological and analytical methods were used to analyze the epidemiological characteristics and the trend of adult mortality in the emergency department of our hospital., Results: Of the 781 selected cases, 448 were male, and 333 were female. Mortality rates were highest in patients aged 80-89 years, and most of the patients were retired (71.57%). Infection disease was associated with the highest mortality rate (44%), followed by cardiovascular disease and malignant tumors., Conclusion: Infectious diseases, cardiovascular diseases, and malignant tumors are the major threats to the lives of patients in the hospital's emergency department. The cause of death differs depending on the patient's age., Key Words: Death, Emergency department, Epidemiological characteristics, Etiology, Retrospective analysis.

Metabolite lactic acid has always been regarded as a metabolic by-product rather than a bioactive molecule. Recently, this view has changed since it was discovered that lactic acid can be used as a signal molecule and has novel signal transduction functions both intracellular and extracellular, which can regulate key functions in the immune system. In recent years, more and more evidence has shown that lactic acid is closely related to the metabolism and polarization of macrophages. During inflammation, lactic acid is a regulator of macrophage metabolism, and it can prevent excessive inflammatory responses; In malignant tumors, lactic acid produced by tumor tissues promotes the polarization of tumor-associated macrophages, which in turn promotes tumor progression. In this review, we examined the relationship between lactic acid and macrophage metabolism. We further discussed how lactic acid plays a role in maintaining the homeostasis of macrophages, as well as the biology of macrophage polarization and the M1/M2 imbalance in human diseases. Potential methods to target lactic acid in the treatment of inflammation and cancer will also be discussed so as to provide new strategies for the treatment of diseases.

Background: IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, and its diagnosis depends mainly on renal biopsy. However, there is no specific treatment for IgAN. Moreover, its causes and underlying molecular events require further exploration., Methods: The expression profiles of GSE64306 and GSE93798 were downloaded from the Gene Expression Omnibus (GEO) database and used to identify the differential expression of miRNAs and genes, respectively. The StarBase and TransmiR databases were employed to predict target genes and transcription factors of the differentially expressed miRNAs (DE-miRNAs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to predict biological functions. A comprehensive analysis of the miRNA-mRNA regulatory network was constructed, and protein-protein interaction (PPI) networks and hub genes were identified. CIBERSORT was used to examine the immune cells in IgAN, and correlation analyses were performed between the hub genes and infiltrating immune cells., Results: Four downregulated miRNAs and 16 upregulated miRNAs were identified. Forty-five and twelve target genes were identified for the upregulated and downregulated DE-miRNAs, respectively. CDKN1A, CDC23, EGR1, HIF1A, and TRIM28 were the hub genes with the highest degrees of connectivity. CIBERSORT revealed increases in the numbers of activated NK cells, M1 and M2 macrophages, CD4 naive T cells, and regulatory T cells in IgAN. Additionally, HIF1A, CDC23, TRIM28, and CDKN1A in IgAN patients were associated with immune cell infiltration., Conclusions: A potential miRNA-mRNA regulatory network contributing to IgAN onset and progression was successfully established. The results of the present study may facilitate the diagnosis and treatment of IgAN by targeting established miRNA-mRNA interaction networks. Infiltrating immune cells may play significant roles in IgAN pathogenesis. Future studies on these immune cells may help guide immunotherapy for IgAN patients., (© 2021. The Author(s).)

Microfluidic spinning technology (MST), incorporating microfluidics with chemical reactions, has gained considerable interest for constructing anisotropic advanced microfibers, especially helical microfibers. However, these efforts suffer from the limited material choices, restricting their applications. Here, a new phase inversion-based microfluidic spinning (PIMS) method is proposed for producing helical microfibers. This method undergoes a physicochemical phase inversion process, which is capable of efficiently manufacturing strong (tensile stress of more than 25 MPa), stretchable, flexible and biocompatible helical microfibers. The helical microfibers can be used to fabricate bi-oriented stretchable artificial abdominal skin, preventing incisional hernia formation and promoting the wound healing without conglutination. This research not only offers a universal approach to design helical microfibers but also provides a new insight into artificial skin., (© 2021 Wiley-VCH GmbH.)

A phytochemical investigation on the flowers of Sophora davidii resulted in the isolation of three unusual matrine-adenine hybrids, sophovicines A-C, together with biogenetically related analogue sophocarpine. Their structures and absolute configurations were determined by NMR analysis, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) data. Since sophovicines represent the first example of matrine-adenine hybrids, a putative biosynthetic pathway toward sophovicines A-C was proposed. In addition, computational molecular modeling suggested that compounds sophovicines B and C may have potent activities against human cytomegalovirus (HCMV). So, the inhibit effects of isolates on HCMV were evaluated. The results show that sophovicines B and C can inhibit HCMV replication effectively with IC 50 values of 7.12 and 7.32 μM, respectively., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Comprising about 82% of the extant fern species diversity, Polypodiales are generally believed to have diversified in the Late Cretaceous. We estimated the divergence times of Polypodiales using both penalized likelihood and Bayesian methods, based on a dataset consisting of 208 plastomes representing all 28 families and 14 fossil constraints reflecting current interpretations of fossil record. Our plastome phylogeny recovered the same six major lineages as a recent nuclear phylogeny, but the position of Dennstaedtiineae was different. The present phylogeny showed high resolution of relationships among the families of Polypodiales, especially among those forming the Aspleniineae. The divergence time estimates supported the most recent common ancestor of Polypodiales and its closest relative dating back to the Triassic, establishment of the major lineages in the Jurassic, and a likely accelerated radiation during the late Jurassic and the Early Cretaceous. The estimated divergence patterns of Polypodiales and angiosperms converge to a scenario in which their main lineages were established simultaneously shortly before the onset of the Cretaceous Terrestrial Revolution, and further suggest a pre-Cretaceous hidden history for both lineages. The pattern of simultaneous diversifications shown here elucidate an important gap in our understanding of the Terrestrial Revolution that shaped today's ecosystems., (© 2021 Willi Hennig Society.)

Dryopteris sect. Diclisodon is a small section of ferns with about 12 species mainly distributed in East Asia. Here, we carried out morphological and phylogenetic analyses of this section. A new species from southwest China, D. gaoligongensis , is described and illustrated. Dryopteris gaoligongensis resembles D. indonesiana and D. sparsa , but differs by having a creeping rhizome and large 4-pinnate fronds. We also show that D. glabrior Ching & Z.Y. Liu is a distinct species; however, because it is a later homonym of D. glabrior Copel., it should be renamed D. renchangiana . We conclude that a species previously known as D. nitidula , also an illegitimate homonym, should be recognized with a new name, D. sinonepalensis . We resolve the phylogenetic position of D. yoroii as sister to other sampled species of D. sect. Diclisodon . Our phylogenetic analyses confirm the distinctiveness of D. gaoligongensis , D. renchangiana , and D. sinonepalensis . A key to species of D. sect. Diclisodon in China is provided., Competing Interests: The authors declare no competing interests., (© 2021 Kunming Institute of Botany, Chinese Academy of Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

To simplify the design of a beam scanning device, we present a simple and compact structure to realize the frequency scanning characteristic based on a hybrid waveguide consisting of a spoof surface plasmon polariton (SSPP) transmission line and half-mode substrate integrated waveguide (HMSIW). Additionally, the radiation characteristic is implemented using periodically modulated slots. The scanning angle range covers backward to forward directions without an open stop band at the broadside. The results from both simulations and measurements show that the total scanning angle reaches 117° for a frequency range of 9-11.4 GHz. Owing to the inherent features of the HMSIW and the unique design of the SSPP transmission line, the entire structure is only 139.2 m m ×15 m m in size. Moreover, the average gain is approximately 6.5 dBi. Overall, the compact size and good performance ensure that the proposed design is favorable for planar integrated communication systems.

Objectives: Thousands of designated COVID-19 hospitals have been set up in China to fight the ongoing COVID-19 pandemic. Anecdotal reports indicate a falling rate of acute stroke diagnoses in these hospitals during the COVID-19 period. We conducted an exploratory single-center analysis to estimate the change in acute stroke presentation at the designated COVID-19 hospitals. Methods: This retrospective observational study included all patients admitted to Yongchuan Hospital Affiliated to Chongqing Medical University with acute stroke between January 24 and March 10, 2020. Patient demographics, characteristics of the stroke, treatment details, and clinical outcomes were compared with those of patients admitted in the corresponding period in the year before (2019, "the pre-COVID-19 period"). Subgroup analysis was performed in the ischemic and hemorrhagic stroke groups. Results: A total of 110 patients presented with acute stroke symptoms during the COVID-19 pandemic, compared with 173 patients in the pre-COVID-19 period. A higher proportion of stroke patients presented to the hospital via emergency medical services during the pandemic (48.2 vs. 31.8%, p = 0.006). There was a lower proportion of ischemic stroke patients (50.9 vs. 65.3%, p = 0.016) than in the preceding year. There were significantly fewer patients with 90-day modified Rankin Scale score ≥3 in the COVID-19 period compared with the pre-COVID-19 period (17.3 vs. 30.6%, p = 0.012). Among patients with ischemic stroke, the mean time from patient arrival to vessel puncture for emergency endovascular therapy in the COVID-19 period was shorter than that in the pre-COVID-19 period (109.18 ± 71.39 vs. 270.50 ± 161.51 min, p = 0.002). Among patients with hemorrhagic stroke, the rate of emergency surgical operation in the COVID-19 period was higher than that in the pre-COVID-19 period (48.1 vs. 30.0%, p = 0.047). The mean time from patient arrival to emergency surgical operation (15.31 ± 22.89 vs. 51.72 ± 40.47 min, p = 0.002) was shorter in the COVID-19 period than in the pre-COVID-19 period. Conclusions: Although fewer acute stroke patients sought medical care in this designated COVID-19 hospital during the COVID-19 pandemic, this type of hospital was more efficient for timely treatment of acute stroke. Recognizing how acute strokes presented in designated COVID-19 hospitals will contribute to appropriate adjustments in strategy for dealing with acute stroke during COVID-19 and future pandemics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tan, Liu, Fan, Du, Wu, Gong, Wei, Zhao, Lei and Zhao.)

Objective: This study aimed to introduce a novel tracheostomy method, the non-guide-wire percutaneous dilatational tracheostomy (NGPDT) technique, and evaluate its effectiveness for critically ill patients undergoing neurosurgery under special conditions., Methods: The clinical data of 48 critically ill patients who underwent NGPDT under special conditions with controlled steps were analyzed retrospectively. The patients' demographic, preoperative state of illness, and diagnosis data were collected. Moreover, their intraoperative and postoperative variables were accessed, e.g., operation times, bleeding, saturation of pulse oxygen (SPO 2 ), and early and late complications related to NGPDT., Results: The mean patient age was 47.7 ± 13.7 years. The mean GCS (Glasgow Coma Scale) was 8.1 ± 2.9, and the mean BMI (Body Mass Index) was 25.2 ± 5.6. There were 38 patients with an endotracheal tube. The mean duration of onset to NGPDT was 4.0 ± 1.3 days. The mean operation time was 4.2 ± 1.9 min. There were 41 patients with mild intraoperative bleeding, 5 with moderate bleeding, and 2 with severe bleeding as well as 46 with mild postoperative bleeding and 2 with moderate bleeding. Additionally, 41 patients required complete extubation after NGPDT. The mean duration of incision healing was 4.8 ± 3.1 days. There was 1 patient with a decrease of SPO 2 ≥ 10%. Three patients presented with a transient violent cough at the primary tracheostomy stage; however, no patients suffered from pneumothorax, subcutaneous emphysema, false passage, or surgery-related death during this procedure., Conclusion: Overall, NGPDT with controlled steps is a fast, safe, and microinvasive procedure. It mildly stimulates the trachea with a low rate of complications., (© 2021. Springer-Verlag GmbH, AT part of Springer Nature.)

A novel Gram-stain-positive, facultatively aerobic, slightly halophilic, endospore-forming bacterium, designated G6-18 T , was isolated from saline soil collected in Yingkou, Liaoning, PR China. Cells of strain G6-18 T grew at 10-37 °C (optimum, 30 °C), at pH 6.0-9.0 (optimum, pH 8.0) and in the presence of 2-15 % (w/v) NaCl (optimum, 5 %). The strain could be clearly distinguished from the related species of the genus Paraliobacillus by its phylogenetic position and biochemical characteristics. It presented MK-7 as the major quinone and the dominant cellular fatty acids were iso-C 16 : 0 , anteiso-C 15 : 0 , C 16 : 0 and iso-C 14 : 0 . The polar lipids consisted of diphosphatidylglycerol and phosphatidylglycerol as the major components. The G+C content of strain G6-18 T genome was 35.3 mol%. 16S rRNA analysis showed that strain G6-18 T had the highest similarity to Paraliobacillus ryukyuensis DSM 15140 T , reaching 97.0 %, followed by Paraliobacillus quinghaiensis CGMCC 1.6333 T with a value of 96.3 %. The average nucleotide identity values between strain G6-18 T and Paraliobacillus ryukyuensis DSM 15140 T , Paraliobacillus sedimins KCTC 33762 T , Paraliobacillus quinghaiensis CGMCC 1.6333 T and Paraliobacillus zengyii DSM 107811 T were 74.3, 72.0, 73.2 and 72.8 %, respectively, and the digital DNA-DNA hybridization values between strain G6-18 T and the neighbouring strains were 15.6, 13.8, 14.2 and 14.2 %, respectively. Based on phenotypic, chemotaxonomic and phylogenetic inferences, strain G6-18 T represents a novel species of the genus Paraliobacillus , for which the name Paraliobacillus salinarum sp. nov. (=CGMCC 1.12058 T =DSM 25428 T ) is proposed.

Frequently calibrating electrochemical biosensors (ECBs) to obtain acceptable accuracy can be cumbersome for the users. Thus, the achievement of calibration-free operation would effectively lead to commercial applications for ECBs in the real world. Herein, we fabricated a temperature-alternated electrochemical aptamer-based (TAEAB) sensor, producing a cycle of "enhanced-responsive and ∼nonresponsive" state at rapidly alternated interface temperatures (5 and 30 °C, respectively). The ratio of peak currents collected at two temperatures overcomes sensor-to-sensor fabrication variations, obviating sensor calibration prior to use due to its good reproducibility. We then demonstrated the capability of TAEAB sensors for improved, sensitive, and calibration-free measurement of different targets within 7 min, which respectively achieved a detection limit of 0.5 μM procaine in undiluted urine and 1.0 μM adenosine triphosphate in undiluted serum. This generalizable approach ameliorates sensitivity without the complicated amplification step, thus simplifying the operation procedure and reducing the detection time, which will effectively improve the clinical utility of biosensors.

Gaultheria fragrantissima (Ericaceae) is an aromatic medicinal plant with high concentrations of the secondarymetabolite methyl salicylate (oil of wintergreen). In this study, the complete chloroplast genomeof G. fragrantissima was sequenced. The complete plastome is 176,196 bp in length, and the GCcontent is 36.6%. The plastome comprises 110 unique genes (76 protein-coding, 30 tRNA and 4 rRNA).Phylogenetic analysis fully supported a sister relationship between G. fragrantissima and G. hookeriwithin the Leucothoides clade of Gaultheria. This chloroplast genome will serve as a valuable referencefor future taxonomic and phylogenetic research., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Gaultheria griffithiana is an evergreen shrub in the family Ericaceae. It is used as a source of the Chinese traditional medicine, Tougucao, with distribution of the junction of eastern Himalaya and Hengduan Mountain. The chloroplast genome of G. griffithiana is 175,649 bp in length with 135 genes, including eight rRNA genes, 39 tRNA genes, and 85 protein-coding genes. Phylogenetic analysis has converged on the placement of G. griffithiana as sister to G. praticola , G. nummularioides , and G. hookeri within the Leucothoides clade of Gaultheria in this study., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

A direct conversion from spoof surface plasmon polaritons (SSPPs) to radiation mode is proposed. A modified parallel two-wire SSPP transmission line is the key to the conversion, which is composed of traditional unit cells with slots among them. Taking advantages of the slots, the phase velocity of electromagnetic waves is larger than that of light, leading to the radiation. Both simulated and measured results show that the radiation occurs from 7.6 to 11 GHz, and the radiation angle keeps nearly stable in the whole operating frequency band, which can be predicted by theoretical calculation. The average gain and efficiency is 6.41 dBi and around 90%, respectively. The simple structure with flexibly tunable operating frequency makes the proposed design promising in planar integrated communication systems.

Carbon quantum dots (CDs) have inspired vast interest because of their excellent photoluminescence (PL) performances and their promising applications in optoelectronic, biomedical, and sensing fields. The development of effective approaches for the large-scale production of CDs may greatly promote the further advancement of their practical applications. In this Minireview, the newly emerging methods for the large-scale production of CDs are summarized, such as microwave, ultrasonic, plasma, magnetic hyperthermia, and microfluidic techniques. The use of the available strategies for constructing CD/polymer composites with intriguing solid-state PL is then described. Particularly, the multiple roles of CDs are emphasized, including as fillers, monomers, and initiators. Moreover, typical applications of CD/polymer composites in light-emitting diodes, fluorescent printing, and biomedicine are outlined. Finally, we discuss current problems and speculate on their future development., (© 2020 Wiley-VCH GmbH.)

In this work, a novel N-doped magnetic mesoporous carbon (NMC) composite (Fe₃O₄/NMC) was synthesized by a two-step process. First, NMC was prepared by a template method using a melamine formaldehyde resin as nitrogen and carbon sources, and then, Fe₃O₄ nanoparticles were loaded into the as-prepared NMC via in-situ coprecipitation process. The morphology, structure, and magnetic properties of Fe₃O₄/NMC were characterized and its adsorption properties were investigated. It can be found that Fe₃O₄/NMC with saturation magnetization of 20 emu · g -1 features a mesoporous structure, and its specific surface area reaches 513 m² · g -1 . These two excellent specificities are propitious to the adsorption and separation of Ag(I) from aqueous solution. The adsorption behavior of Fe₃O₄/NMC nanocomposite has been investigated by adsorption kinetics and isotherms adsorption analyses as well. The adsorption isotherm and the adsorption kinetics of Ag(I) onto Fe₃O₄/NMC agrees well with Langmuir model and pseudo-second-order model, respectively. Moreover, the Fe₃O₄/NMC was easily to recovery by applied magnetic field, the adsorption capacity of Fe₃O₄/NMC was about 90.3% of the initial saturation adsorption capacity after five continuous uses.

The rat auditory cortex is divided anatomically into several areas, but little is known about the functional differences in information processing among these areas. Three tonotopically organized core fields, namely, the primary (A1), anterior (AAF), and ventral (VAF) auditory fields, as well as one non-tonotopically organized belt field, the dorsal belt (DB), were identified based on their response properties. Compared to neurons in A1, AAF and VAF, units in the DB exhibited little or no response to pure tones but strong responses to white noise. The few DB neurons responded to pure tones with thresholds greater than 60 dB SPL, which was significantly higher than the thresholds of neurons in the core regions. In response to white noise, units in DB showed significantly longer latency and lower peak response, as well as longer response duration, than those in the core regions. Responses to repeated white noise were also examined. In contrast to neurons in A1, AAF and VAF, DB neurons could not follow repeated stimulation at a 300 ms inter-stimulus interval (ISI) and showed a significant steeper ISI tuning curve slope when the ISI was increased from 300 ms to 4.8 s. These results indicate that the DB processes auditory information on broader spectral and longer temporal scales than the core regions, reflecting a distinct role in the hierarchical cortical pathway., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Aldehyde dehydrogenase-2 (ALDH2) plays an important role in the alcohol detoxification and acetaldehyde metabolism. Published studies have demonstrated some inconsistent associations between ALDH2 rs671 G>A polymorphism and head and neck cancer (HNC) risk., Methods: A meta-analysis was performed to provide pooled data on the association between the ALDH2 rs671 G>A polymorphism and HNC risk. Electronic databases were searched to identify relevant studies. Odds ratios and 95% confidence intervals (CIs) were used to examine the pooled effect size of each genetic model. In addition, heterogeneity test, accumulative analysis, sensitivity analysis, and publication bias were conducted to test the statistical power., Results: Thirteen publications (14 independent case-control studies) involving 10,939 subjects were selected. The stratified analysis indicated that both light/moderated drinking (e.g., GA vs. GG: OR = 1.47, 95% CI = 1.16 to 1.86, p < 0.01, I 2  = 81.1%) and heavy drinking would increase HNC risk with rs671 G>A mutation (e.g., GA vs. GG: OR = 2.30, 95% CI = 1.11 to 4.77, p = 0.03, I 2  = 81.9%)., Conclusions: In summary, this meta-analysis suggested that the ALDH2 rs671 G>A polymorphism may play an important synergistic effect in the pathogenesis of HNC development in East Asians., (© 2020 by the Research Society on Alcoholism.)

Background: Horizontal gene transfer (HGT) has been documented in many herbivorous insects, conferring the ability to digest plant material and promoting their remarkable ecological diversification. Previous reports suggest HGT of antibacterial enzymes may have contributed to the insect immune response and limit bacterial growth. Carnivorous insects also display many evolutionary successful lineages, but in contrast to the plant feeders, the potential role of HGTs has been less well-studied., Results: Using genomic and transcriptomic data from 38 species of ladybird beetles, we identified a set of bacterial cell wall hydrolase (cwh) genes acquired by this group of beetles. Infection with Bacillus subtilis led to upregulated expression of these ladybird cwh genes, and their recombinantly produced proteins limited bacterial proliferation. Moreover, RNAi-mediated cwh knockdown led to downregulation of other antibacterial genes, indicating a role in antibacterial immune defense. cwh genes are rare in eukaryotes, but have been maintained in all tested Coccinellinae species, suggesting that this putative immune-related HGT event played a role in the evolution of this speciose subfamily of predominant predatory ladybirds., Conclusion: Our work demonstrates that, in a manner analogous to HGT-facilitated plant feeding, enhanced immunity through HGT might have played a key role in the prey adaptation and niche expansion that promoted the diversification of carnivorous beetle lineages. We believe that this represents the first example of immune-related HGT in carnivorous insects with an association with a subsequent successful species radiation.

Soil contamination by arsenic (As) is an important environmental issue globally. Intercropping of hyperaccumulators with main crop is typically applied for remediation of As-contaminated soil. Most hyperaccumulators are wild plants with small biomass and slow growth rates. Thus, remediation is slow. Here, we propose an effective intercropping system for remediation of As-contaminated paddy soil. Four treatments-intercropping with water spinach ( Ipomoea aquatica Forsk) (T1), water celery ( Oenanthe javanica (Blume) DC.) (T2), or Guangdong white arrowhead ( Sagittaria sagittifolia L. var) (T3), with rice ( Oryza sativa L.) monoculture (control, CK)-were used. Compared with the CK, grain yield per plant of rice under T1 and T2 increased by 58.13% and 10.48%, respectively, but decreased by 46.90% in T3. As concentration, bioaccumulation factor, and translocation factor in brown rice were significantly lower in the intercropping treatments than in CK. As removal by water spinach was 7.04 and 1.47 times that by water celery and arrowhead, respectively. The pH of paddy soil was significantly higher in all treatments than in CK, and iron plaque on rice roots under T1 and T2 decreased significantly but increased significantly under T3 compared with that of CK. Rice intercropped with water spinach had the best remediation effect. Novelty Statement: We believe that the following highlights of this manuscript will make it interesting to general readers of this journal.First, in recent years, many articles about intercropping system for the remediation of soil heavy metal pollution focus on dry land, and few studies have focused on paddy soil. The present study was on arsenic-contaminated paddy soil remediation.Second, water spinach, water celery, and arrowhead have great potential for phytoremediation. Studies have shown that these three aquatic vegetables play a role in the removal of certain pollutants, such as heavy metals. Moreover, when intercropped with rice, they can effectively increase rice yield and reduce rice diseases and insect pests. However, studies on remediation of arsenic-contaminated soil by intercropping aquatic vegetables and rice have not been reported. We propose here a rice-aquatic vegetables (water spinach, water celery and arrowhead) intercropping pattern for remediation of arsenic in soil.Third, according to the arsenic concentration and removal rate, we used a bioaccumulation factor, translocation factor, and arsenic removal per unit area of plants for the quantitative evaluation of the remediation effects of the intercropping systems. We found that the intercropping of rice and water spinach could be used to remediate arsenic-contaminated soil. Moreover, the extraction contents of arsenic using intercropping with water spinach was higher than that achieved in a previous study that applied intercropping with the arsenic hyperaccumulator Pteris vittata over the same growth time. This study provides a reference for realizing both remediation and increased production in arsenic-contaminated soil and for promoting sustainable development of agriculture.

Objective: To investigate the effects of orthokeratology on biological parameters and visual quality of adolescents with low-grade corneal astigmatism myopia., Patients and Methods: In this study, a total of 41 myopic adolescents were prescribed with orthokeratology glasses in our hospital from February 2018 to March 2019 and voluntarily cooperated with relevant examinations before and after wearing orthokeratology lenses. Patients' uncorrected distant visual acuity (UCVA-D), uncorrected near visual acuity (UCVA-N) and naked eye near stereoacuity before wearing glasses, 1 month, and 3 months after wearing glasses were observed. The corneal astigmatism of patients was observed. The corneal endothelial cell density was observed. The dynamic adjustment function (NP, AF, NRA, PRA) values of patients were observed. The comparison of biological indexes in different time periods was observed. The changes of corneal curvature before wearing orthokeratology lens, 1 month and 3 months after wearing orthokeratology lens were observed., Results: There were significant changes of patients 1 month after wearing orthokeratology lenses (p < 0.05), while there was no significant difference between 3 months after wearing the orthokeratology lenses and 1 month after wearing the orthokeratology lenses (p < 0.05). Patients' NCAV-D and UCVA-N were recorded by a conversion method of 5 points. There were differences in the NCVA-D, NCVA-N, naked eye near stereoacuity before, 1 month, and 3 months after wearing glasses (p < 0.05). By observing patients' biological indicators and dynamic adjustment, it was found that there were statistically significant differences in NP, AF, BRA and PRA before wearing the glasses, 1 month and 3 months after wearing the glasses (p < 0.05)., Conclusions: The use of orthokeratology can greatly correct myopia patients' vision, improve their stereoscopic vision, control the progression of myopia, and improve their eye regulation, which is of high safety and great short-term effect.

α-synuclein (α-syn) is a protein associated with the pathogenesis of Parkinson's disease (PD), the second most common neurodegeneration disease with no effective treatment. However, how α-syn drives the pathology of PD remains elusive. Recent studies suggest that α-syn oligomers are the primary cause of neurotoxicity and play a critical role in PD. In this review, we discuss the process of α-syn oligomers formation and the current understanding of the structures of oligomers. We also describe seed and propagation effects of oligomeric forms of α-syn. Then, we summarize the mechanism by which α-syn oligomers exert neurotoxicity and promote neurodegeneration, including mitochondrial dysfunction, endoplasmic reticulum stress, proteostasis dysregulation, synaptic impairment, cell apoptosis and neuroinflammation. Finally, we investigate treatment regimens targeting α-syn oligomers at present. Further research is needed to understand the structure and toxicity mechanism of different types of oligomers, so as to provide theoretical basis for the treatment of PD.

Macroscopic self-assembly has increasingly attracted numerous concerns because of the facile fabrication of complex structures and diversified morphologies. Key challenges still remain to design high-performance building blocks to increase the efficiency and diversity of macroscopic self-assembly. Here, we designed triple noncovalent interactions (carboxyl-Zn 2+ coordination, host-guest interactions, and hydrogen bonding interactions) to enhance the interactions between self-healing fibers, constructing multidimensional nonwoven fiber-based fabrics through macroscopic self-assembly without further postprocessing. Profiled from the strong interactions generated from triple noncovalent interactions, ordered two-dimensional plane and three-dimensional spiral gel fabrics were fabricated using polyvinyl pyrrolidone/gel-based fibers as building blocks toward a human motion sensor. Moreover, we demonstrated that the macroscopic self-assembly strategy is universal to construct three-dimensional film-based fabrics toward wound dressing based on the triple noncovalent interactions between two-dimensional films. This macroscopic self-assembly approach provides an alternative strategy to fabricate gel fabrics for various applications.

N,C-chelate organoboron compounds are widely employed as photoresponsive and optoelectronic materials due to their efficient photochromic reactivity. It was found in experiments that two diphenyl-substituted organoboron compounds, namely B(ppy)Ph 2 (ppy=2-phenylpyridyl) and B(iba)Ph 2 (iba=N-isopropylbenzylideneamine), show distinct photochemical reactivity. B(ppy)Ph 2 is inert on irradiation, whereas B(iba)Ph 2 undergoes photoinduced transformations, yielding BN-cyclohepta-1,3,5-triene via a borirane intermediate. In this work, the complete active space self-consistent field and its second-order perturbation (CASPT2//CASSCF) methods were used to investigate the photoinduced reaction mechanisms of B(ppy)Ph 2 and B(iba)Ph 2 . The calculations showed that the two compounds isomerize to borirane in the same way by passing a transition state in the S 1 state and a conical intersection between the S 1 and S 0 states. The energy barriers in the S 1 state of 0.54 and 0.26 eV for B(ppy)Ph 2 and B(iba)Ph 2 , respectively, were explained by analyzing the charge distributions of minima in S 0 and S 1 states. The results provide helpful insights into the excited-state dynamics of organoboron compounds, which could assist in rational design of boron-based photoresponsive materials., (© 2020 Wiley-VCH GmbH.)

Background: Dysfunction of apoptosis is a significant characteristic in chronic lymphocytic leukemia (CLL). Murine double minute 4 (MDM4), miR-34a and TP53 are found to participate in modulating cellular apoptosis while the specific mechanism keeps unclear. This study was designed to investigate the potential feedback circuit among MDM4, miR-34a and TP53., Methods: According to the bioinformatic approaches, there are 4 miR-34a candidate binding domains in MDM4. Use dual luciferase reporter gene to verify the regulation between miR-34a and MDM4. Flow cytometry was used to detect the change of apoptosis level in CLL cells before and after miR-34a mimics and shMDM4 were respectively transfected into primary CLL cells in vitro. Meanwhile, Real-time PCR was used to detect the change of RNA expression of MDM4, miR-34a and TP53., Results: Up-regulated expression of miR-34a or down-regulated expression of MDM4 could increase apoptosis of CLL cells, inhibit expression of MDM4 and decrease expression of p53 in mRNA level compared to negative control (NC) or shNC (P<0.05). The luminescence of psiCHECK-2-MDM4 EXON 11 can be effectively inhibited by miR-34a (P<0.05)., Conclusions: MiR-34a could modulate MDM4 by binding to MDM4 exon 11 instead of 3'UTR. This research thus highlights a forceful evidence for miR-34a/MDM4/p53 feedback circuit in CLL apoptosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr-20-1710). The authors have no conflicts of interest to declare., (2020 Translational Cancer Research. All rights reserved.)

Paraneoplastic pemphigus (PNP) is a severe autoimmune syndrome commonly triggered by neoplasms. The prognosis of CLL-associated PNP is dismal due to its refractory course and secondary infection and no standard treatment was recommended. We retrospectively reported six CLL with PNP cases from 842 cases of CLL including diagnosis, treatment and prognosis. The median time between the initial of CLL to PNP was 36 months while the median overall survival from the diagnosis of PNP was 26 months. And three cases died of lung infection while 5 developed pulmonary symptoms. And 5 cases received fludarabine-based chemotherapy before developing PNP, which suggesting fludarabine was one of potential causes of PNP. For the treatment, five patients were rescued by combined regimens including rituximab, methylprednisolone, immunoglobulin, fresh frozen plasma and the last received ibrutinib combined with short-term prednisone. Fludarabine-based regimen may be one of the potential causes of PNP. The combined regimen might shed a new light, while ibrutinib is a promising drug for CLL with PNP, but needs much more evidence. PNP should be carefully treated to guide early diagnosis and intervention for a better prognosis.

We describe a photoinduced copper-catalyzed asymmetric radical decarboxylative alkynylation of bench-stable N-hydroxyphthalimide(NHP)-type esters of racemic alkyl carboxylic acids with terminal alkynes, which provides a flexible platform for the construction of chiral C(sp 3 )-C(sp) bonds. Critical to the success of this process are not only the use of the copper catalyst as a dual photo- and cross-coupling catalyst but also tuning of the NHP-type esters to inhibit the facile homodimerization of the alkyl radical and terminal alkyne, respectively. Owing to the use of stable and easily available NHP-type esters, the reaction features a broader substrate scope compared with reactions using the alkyl halide counterparts, covering (hetero)benzyl-, allyl-, and aminocarbonyl-substituted carboxylic acid derivatives, and (hetero)aryl and alkyl as well as silyl alkynes, thus providing a vital complementary approach to the previously reported method., (© 2020 Wiley-VCH GmbH.)

Objective: This study aimed to determine the effect of parathyroid hormone-related protein (PTHrP) on proliferation of cardiac fibroblasts (CFs) in primary cultures of neonatal Wistar rats., Methods: Different PTHrP concentrations were added to CFs of neonatal Wistar rats and the cells were grouped according to the concentrations added. A verapamil (VPL) group and a calcitriol (CAL) group were also established. Changes in cell proliferation and in cyclic adenosine monophosphate and calcium ion levels were identified and recorded., Results: We found that as the concentration of PTHrP increased, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT, a tetrazolium salt) colorimetric absorbance values (A values) decreased. These values in the PTHrP groups were significantly lower than those in the control group. MTT colorimetric A values and 3 H-thymidine deoxyribose intake were lower in the VPL group, low-dose CAL group, and the PTHrP 10 -7 mol/L group compared with the control group. However, MTT colorimetric A values and 3 H-thymidine deoxyribose intake were higher in the high-dose CAL group than in the PTHrP 10 -7 mol/L group. As PTHrP concentrations increased, intracellular cyclic adenosine monophosphate concentrations also increased., Conclusion: PTHrp, VPL, and low-dose CAL inhibit proliferation of CFs, while high-dose CAL promotes proliferation of CFs.