CncC-Keap1-P450s pathway is involved in the detoxification of emamectin benzoate in the spongy moth Lymantria dispar.

The detoxification of insecticides in insects is dependent on the expression and activity of multiple detoxification enzymes. As an important modulator of detoxification enzymes, the CncC-Keap1 pathway was involved in the detoxification of various pesticides. However, whether the CncC-Keap1 pathway is involved in the detoxification of emamectin benzoate (EMB) is unclear. In this study, we cloned the LdCncC and LdKeap1 from spongy moths (Lymantria dispar). Our results showed that EMB exposure induced oxidative stress, and activated the CncC-Keap1 pathway at mRNA and protein levels. Removing ROS by N-acetylcysteine remarkably decreased H2O2 levels and restored the expression of LdCncC and LdKeap1. The silencing LdCncC, not LdKeap1, by dsRNA significantly decreased the cytochrome P450 activities, and increased the sensitivity of larvae to EMB. Besides, the expression of CYP6B7v1, CYP321A7 and CYP4S4v1 were significantly decreased after silencing LdCncC. Notably, the knockdown of CYP6B7v1, CYP321A7 or CYP4S4v1 significantly increased the mortality induced by EMB exposure. Therefore, we proposed that activation of CncC-Keap1 pathway induced by ROS increased the detoxification of EMB in spongy moths by regulating the expression of CYP6B7v1, CYP321A7 and CYP4S4v1. Our study strengthened the understanding of the detoxification of EMB from the perspective of CncC-Keap1-P450s pathway.

Chromosome-level genome assembly of the Asian spongy moths Lymantria dispar asiatica.

The Asian spongy moth, Lymantria dispar asiatica, is one of the most devastating forestry defoliators. The absence of a high-quality genome limited the understanding of its adaptive evolution. Here, we conducted the first chromosome-level genome assembly of L. dispar asiatica using PacBio HIFI long reads, Hi-C sequencing reads and transcriptomic data. The total assembly size is 997.59 Mb, containing 32 chromosomes with a GC content of 38.91% and a scaffold N50 length of 35.42 Mb. The BUSCO assessment indicated a completeness estimate of 99.4% for this assembly. A total of 19,532 protein-coding genes was predicted. Our study provides a valuable genomics resource for studying the mechanisms of adaptive evolution and facilitate an efficient control of L. dispar asiatica.

Heteroplasmy and Individual Mitogene Pools: Characteristics and Potential Roles in Ecological Studies.

The mitochondrial genome (mitogenome or mtDNA), the extrachromosomal genome, is a multicopy circular DNA with high mutation rates due to replication and repair errors. A mitochondrion, cell, tissue, organ, or an individual body may hold multiple variants, both inherited and developed over a lifetime, which make up individual mitogene pools. This phenomenon is also called mtDNA heteroplasmy. MtDNA variants influence cellular and tissular functions and are consequently subjected to selection. Although it has long been recognized that only inheritable germline heteroplasmies have evolutionary significance, non-inheritable somatic heteroplasmies have been overlooked since they directly affect individual fitness and thus indirectly affect the fate of heritable germline variants. This review focuses on the characteristics, dynamics, and functions of mtDNA heteroplasmy and proposes the concept of individual mitogene pools to discuss individual genetic diversity from multiple angles. We provide a unique perspective on the relationship between individual genetic diversity and heritable genetic diversity and guide how the individual mitogene pool with novel genetic markers can be applied to ecological research.

Molecular surveillance of chloroquine resistance in Plasmodium vivax isolates from malaria cases in Yunnan Province of China using pvcrt-o gene polymorphisms.

BACKGROUND: The efficacy of chloroquine treatment for vivax malaria has been rarely evaluated due to a lack of an appropriate testing method. The objective of this study was to conduct molecular monitoring of chloroquine resistance in Plasmodium vivax strains from vivax malaria patients in Yunnan Province, focusing on the analysis of polymorphism in the P. vivax chloroquine resistance transporter protein orthologous gene (pvcrt-o). METHODS: In accordance with the principles of a cohort study, blood samples were collected from malaria cases diagnosed with a P. vivax mono-infection in Yunnan Province from 2020 to 2022. Segmental PCR was used to amplify the whole pvcrt-o gene in the blood samples and their products were subsequently sequenced. The sequencing data were arranged to obtain the full coding DNA sequence (CDS) as well as the gene's promoter region sequences. The CDSs were aligned with the reference sequence (XM_001613407.1) of the P. vivax SalI isolate to identify the mutant loci. RESULTS: From a total of 375 blood samples taken from vivax malaria cases, 272 both whole gene CDSs (1272-1275 bp) and promoter DNA sequences (707 bp) of pvcrt-o gene were obtained. Among the whole CDSs, there were 7 single nucleotide polymorphic sites in which c.7 A>G was the minor allele frequency (MAF) site with 4.4% (12/272) detection rate. The mutation detection rate showed a significant decrease from 9.8% (10/102) in 2020 to 1.1% (1/92) in 2021 and 1.3% (1/78) in 2022, indicating statistical significance (χ2 = 11.256, P < 0.05). Among the identified 12 haplotypes, the majority of which were wild type (75.7%; 206/272). These four mutant haplotypes (Hap_3, Hap_5, Hap_9, and Hap_10) were classified as "K10 insertion type" and accounted for 12.1% (33/272). The detection rate of Hap_3 increased from 1.0% (1/102) in 2020 to 13.0% (12/92) in 2021 and 14.1% (11/78) in 2022, indicating statistical significance. A total of 23.8% (65/272) of the samples exhibited 14 bp (bp) deletions in the promoter region, occurring most frequently in the wild type haplotype (Hap_1) samples at a rate of 28.6% (59/206). CONCLUSIONS: In recent years in Yunnan Province, a notable proportion of vivax malaria patients are infected by P. vivax strains with a "K10 insertion" and partial sequence deletions in the promoter region of the pvcrt-o gene, necessitating vigilance.

The genome assembly and annotation of the many-banded krait, Bungarus multicinctus.

Snakes are a vital component of wildlife resources and are widely distributed across the globe. The many-banded krait Bungarus multicinctus is a highly venomous snake found across Southern Asia and central and southern China. Snakes are an ancient reptile group, and their genomes can provide important clues for understanding the evolutionary history of reptiles. Additionally, genomic resources play a crucial role in comprehending the evolution of all species. However, snake genomic resources are still scarce. Here, we present a highly contiguous genome of B. multicinctus with a size of 1.51 Gb. The genome contains a repeat content of 40.15%, with a total length exceeding 620 Mb. Additionally, we annotated a total of 24,869 functional genes. This research is of great significance for comprehending the evolution of B. multicinctus and provides genomic information on the genes involved in venom gland functions.

Characteristics of molecular markers associated with chloroquine resistance in Plasmodium vivax strains from vivax malaria cases in Yunnan Province, China.

BACKGROUND: Chloroquine (CQ) has been the preferred clinical treatment for vivax malaria in Yunnan Province since 1958, with over 300,000 patients. This study aimed to help make trend predictions regarding variations the in anti-malarial drug susceptibility of Plasmodium vivax distributed in Yunnan Province and effectively implement monitoring measures on the efficacy of anti-malarial drugs for vivax malaria. METHODS: Blood samples collected from patients with mono-P. vivax infections were employed in this study based on the principle of cluster sampling. The whole gene of P. vivax multidrug resistance 1 protein gene (pvmdr1) was amplified by nested-PCR techniques and the PCR amplification produce were sequenced by Sanger bidirectional sequencing. The mutant loci and haplotypes of coding DNA sequence (CDS) were identified by comparison with the reference sequence (NC_009915.1) of the P. vivax Sal I isolate. Parameters such as Ka/Ks ratio were calculated using MEGA 5.04 software. RESULTS: A total of 753 blood samples from patients infected with mono-P. vivax were collected, of which 624 blood samples yielded the full gene sequence (4392 bp) of the pvmdr1 gene, with 283, 140, 119, and 82 sequences from 2014, 2020, 2021 and 2022, respectively. A total of 52 single nucleotide polymorphic (SNP) loci were detected for the 624 CDSs, of which 92.3% (48/52), 34.6% (18/52), 42.3% (22/52), and 36.5% (19/52) SNPs were detected in 2014, 2020, 2021 and 2022, respectively. All of 624 CDSs were defined for a total of 105 mutant haplotypes, with CDSs of 2014, 2020, 2021, and 2022 containing 88, 15, 21, and 13 haplotypes, respectively. Of the 105 haplotypes, the threefold mutant haplotype (Hap_87) was the starting point for stepwise evolution, and the most drastic tenfold mutations were Hap_14 and Hap_78, and the fivefold, sixfold, sevenfold, and eightfold mutations. CONCLUSIONS: In the majority of vivax malaria cases in Yunnan Province, most of them were infected with strains carrying demonstrating highly mutated in pvmdr1 genes. However, the dominant mutation strains types varied from year to year, which warrants further exploration in order to confirm the correlation between with phenotypic changes in P. vivax strains and their susceptibility to anti-malarial drugs such as chloroquine.

The evolutionary dynamics history of canine distemper virus through analysis of the hemagglutinin gene during 1930-2020.

Canine distemper virus (CDV) is a lethal viral disease of carnivores which is considered to be a serious threat to domestic and wild species. Despite the widespread use of vaccines, CDV still occurs in vaccinated animals and current vaccines does not guarantee complete protection. In this study, a total of 286 hemagglutinin (H) gene sequences of the virus isolated in 25 countries during 90 years (1930-2020) were analyzed by Bayesian maximum likelihood analysis to estimate the population dynamics. We identified the most recent common ancestor (TMRCA) of the virus in 1868 in the USA which arrived in continental Europe in 1948, and from there, the virus spread rapidly to other continents. The Canidae family was identified as the original host as well as a source of the subsequent spread. We identified 11 lineages of geographic co-circulating strains globally. The effective population size experienced a two-phase-exponential growth between 2000-2005 and 2010-2012. Our findings provide a novel insight into the epidemic history of canine distemper virus which may facilitate more effective disease management. This study uses a large set of sequencing data on the H gene of CDV to identify distinct lineages of the virus, track its geographic spread over time, analyze its likelihood of transmission within and between animal families, and provide suggestions for improved strategies to combat the virus. Supplementary Information: The online version contains supplementary material available at 10.1007/s10344-023-01685-z.

Risk factors of immune checkpoint inhibitor-associated acute kidney injury: evidence from clinical studies and FDA pharmacovigilance database.

BACKGROUND: Several risk factors of immune checkpoint inhibitors (ICIs)-associated acute kidney injury (AKI) have been reported sporadically. To identify the risk factors of ICIs-associated AKI in a large-scale population, therefore we conducted a systematic review and a real-world retrospective study. METHODS: We search literature concerning risk factors of ICIs-associated AKI in ClinicalTrials.gov and electronic databases (PubMed, Cochrane Library, Embase) up to January 2022. Meta-analysis was performed by using odds ratios (ORs) with 95%CIs. In a separate retrospective pharmacovigilance study by extracting data from US FDA Adverse Event Reporting System (FAERS) database, disproportionality was analyzed using the reporting odds ratio (ROR). RESULTS: A total of 9 studies (5927 patients) were included in the meta-analysis. The following factors were associated with increased risk of ICIs-associated AKI, including proton pump inhibitors(PPIs) (OR = 2.07, 95%CI 1.78-2.42), angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin receptor blockers (ARBs) (OR = 1.56, 95%CI 1.24-1.95), nonsteroidal anti-inflammatory drugs (NSAIDs) (OR = 1.29, 95%CI 1.01-1.65), diuretics (OR = 2.00, 95%CI 1.38-2.89), diabetes mellitus (OR = 1.28, 95%CI 1.04-1.57), genitourinary cancer (OR = 1.46, 95%CI 1.15-1.85), combination therapy of ICIs (OR = 1.93, 95%CI 1.25-2.97) and extrarenal immune-related adverse events(irAEs) (OR = 2.51, 95%CI 1.96-3.20). Furthermore, analysis from FAERS database verified that concurrent exposures of PPIs (ROR = 2.10, 95%CI 1.91-2.31), ACEIs/ARBs (ROR = 3.25, 95%CI 2.95-3.57), NSAIDs (ROR = 3.06, 95%CI 2.81-3.32) or diuretics (ROR = 2.82, 95%CI 2.50-3.19) were observed significant signals associated with AKI in ICIs-treated patients. CONCLUSIONS: Concurrent exposures of PPIs, ACEIs/ARBs, NSAIDs or diuretics, diabetes mellitus, genitourinary cancer, combination therapy, and extrarenal irAEs seem to increase the risk of AKI in ICIs-treated patients.

High serum immunoglobulin D levels in systemic lupus erythematosus: more to be found?

INTRODUCTION: Many studies have shown that serum immunoglobulin D (IgD) is usually increased in autoimmune diseases. The potential role of IgD in systemic lupus erythematosus (SLE) is still unclear. Our study aimed to compare the serum IgD levels of SLE with different population and to evaluate the relationship between serum IgD and SLE. METHODS: Fifty SLE patients, 40 non-SLE chronic kidney disease (CKD) patients, and 50 healthy volunteers were enrolled in this study. Serum IgD levels were analyzed by ELISA assay and compared between groups. The correlation of serum IgD and SLE disease were evaluated. The ability of serum IgD to predict SLE was analyzed by graphing receiver operating characteristic curves. RESULTS: Serum IgD levels were significantly higher in SLE patients compared to non-SLE CKD and healthy controls (7436.1 ± 5862.1 vs. 4517.8 ± 5255.2 vs. 4180.4 ± 4881 ng/mL, p = 0.01, p = 0.002, respectively), and in patients with high SLE Disease Activity Index (SLEDAI) scores compared with those with low scores (8572.9 ± 5968.7 vs. 5020.4 ± 4972.5 ng/mL, p = 0.044). High level of inflammatory cytokines and decreased circulating basophil counts were found in SLE patients (p < 0.05). No correlations was identified between serum IgD levels and SLEDAI scores (p > 0.05). Serum IgD was noninferior to IgG or IgE in discriminating SLE with an area under the curve of 0.672 (95% CI, 0.59-0.75). CONCLUSIONS: Serum IgD levels are significantly elevated in SLE patients with high SLEDAI scores. Simultaneous occurrence of increased inflammatory cytokines and decreased basophil counts highlights the potential role of IgD-targets interaction in SLE pathogenesis. Key points • Total serum IgD levels were elevated in SLE patients. • High IgD levels were significantly higher in SLE patients with high SLEDAI scores. • The ability of serum IgD was equivalent to IgG or IgE in discriminating SLE from CKD and healthy adult.

Molecular identification of vivax malaria relapse patients in the Yunnan Province based on homology analysis of the Plasmodium vivax circumsporozoite protein gene.

More than 85% of the malaria burden in the Yunnan Province is caused by imported vivax malaria, and Yunnan is also where the majority of vivax malaria patients are diagnosed in China. Timely removal of the infection sources of Plasmodium vivax and its breeding environment remains the key to eliminating the secondary transmission of imported malaria. To that end, blood samples were collected from cases diagnosed and revalidated as single species infection with P. vivax in the Yunnan Province from 2013 to 2020. Specifically, samples from vivax malaria patients with suspected relapses episodes were subjected to PCR amplification, product sequencing, and analysis of the P. vivax circumsporozoite protein (pvcsp) gene. In total, 77 suspected relapse patients were identified out of 2484 cases infected with P. vivax, with a total of 81 recurrent episodes. A total of 156 CDS (coding DNA sequence) chains were obtained through PCR amplification and sequencing of the pvcsp gene from 159 blood samples, 121 of which can be matched to the paired sequences of 59 vivax malaria patients with both primary attack and recurrent experience. Of the 59 pairs of pvcsp gene sequences, every one of 31 pairs showed only one haplotype and no variant sites (VS), meaning every two paired sequence was completely homologous. Every one of the remaining 28 paired sequences had two haplotypes but no length polymorphism, indicating that the paired sequences was "weakly heterologous" with no fragment insertions (or deletions). All 59 vivax malaria patients with recurrences were caused by the activation of P. vivax hypnozoites originated from the same population as the primary infection. The paired analysis of the similarity between high variant genes allowed the identification of relapse episodes caused by P. vivax homologous hypnozoites and also demonstrated pvcsp gene as one of the candidate molecular markers for tracing infection origin.

Chromosome-scale genomes reveal genomic consequences of inbreeding in the South China tiger: A comparative study with the Amur tiger.

The South China tiger (Panthera tigris amoyensis, SCT) is the most critically endangered subspecies of tiger due to functional extinction in the wild. Inbreeding depression is observed among the captive population descended from six wild ancestors, resulting in high juvenile mortality and low reproduction. We assembled and characterized the first SCT genome and an improved Amur tiger (P. t. altaica, AT) genome named AmyTig1.0 and PanTig2.0. The two genomes are the most continuous and comprehensive among any tiger genomes yet reported at the chromosomal level. By using the two genomes and resequencing data of 15 SCT and 13 AT individuals, we investigated the genomic signature of inbreeding depression of the SCT. The results indicated that the effective population size of SCT experienced three phases of decline, ~5.0-1.0 thousand years ago, 100 years ago, and since captive breeding in 1963. We found 43 long runs of homozygosity fragments that were shared by all individuals in the SCT population and covered a total length of 20.63% in the SCT genome. We also detected a large proportion of identical-by-descent segments across the genome in the SCT population, especially on ChrB4. Deleterious nonsynonymous single nucleotide polymorphic sites and loss-of-function mutations were found across genomes with extensive potential influences, despite a proportion of these loads having been purged by inbreeding depression. Our research provides an invaluable resource for the formulation of genetic management policies for the South China tiger such as developing genome-based breeding and genetic rescue strategy.

The chromosome-scale genome of the raccoon dog: Insights into its evolutionary characteristics.

The raccoon dog (Nyctereutes procyonoides) is an invasive canid species native to East Asia with several distinct characteristics. Here, we report a chromosome-scale genome of the raccoon dog with high contiguity, completeness, and accuracy. The intact taste receptor genes, expanded gene families, and positively selected genes related to digestion, absorption, foraging, and detoxification likely support the omnivory of raccoon dogs. Several positively selected genes and raccoon dog-specific mutations in TDRD6 and ZP3 genes may explain their high reproductivity. Enriched GO terms in energy metabolism and positively selected immune genes were speculated to be closely related to the diverse immune system of raccoon dogs. In addition, we found that several expanded gene families and positively selected genes related to lipid metabolism and insulin resistance may contribute to winter sleep of the raccoon dog. This high-quality genome provides a valuable resource for understanding the evolutionary characteristics of this species.

Serum homocysteine is associated with tubular interstitial lesions at the early stage of IgA nephropathy.

BACKGROUND: The association between homocysteine (Hcy) and IgA nephropathy (IgAN) is not well understood. We aimed to investigate the relationship between Hcy and clinicopathologic features in IgAN patients. METHODS: A total of 337 IgAN patients and 150 sex- and age- matched healthy controls were enrolled in this single-center retrospective study. According to Hcy ≤ 10 µmol/L or > 10 µmol/L, patients were divided into low and high Hcy groups. Multivariate logistic regression was performed to explore the risk factors for elevated Hcy. RESULTS: Serum Hcy was higher in IgAN patients than in healthy controls [11.6 (9.1,15.3) vs. 8.8 (7.5,10.6) µmol/L, P < 0.001], unanimously in the subgroup of 156 patients with a normal estimated glomerular filtration rate (eGFR) (≥ 90 ml/min/1.73 m2) [9.9 (7.6,12.4) vs. 8.8 (7.5,10.6) µmol/L, P < 0.001]. Compared to the low Hcy group, serum creatinine (Scr), blood urine nitrogen (BUN), uric acid (UA), endocapillary hypercellularity (E) and tubular atrophy/interstitial fibrosis lesion (T) were higher in the high Hcy group. Hcy levels were positively correlated with Scr, BUN, UA, 24-h urine protein, and E and T lesions, but negatively correlated with eGFR and superoxide dismutase (SOD). In the subgroup with normal eGFR, patients with higher Hcy were persistent with higher Scr, BUN and T lesions. A multivariate logistic regression model showed that the risk of elevated Hcy in patients with pathological T increased by 2.87-fold. T lesions could better predict high Hcy, with an odds ratio (OR) of 14.20 in the subgroup with normal eGFR. CONCLUSIONS: Pathologic T was an independent risk factor associated with elevated Hcy, especially at the early stage of IgAN.

Chromosome-Level Genome Assembly of the Green Peafowl (Pavo muticus).

The green peafowl (Pavo muticus) is facing a high risk of extinction due to the long-term and widespread threats of poaching and habitat conversion. Here, we present a high-quality chromosome-level genome assembly of the green peafowl with high contiguity and accuracy assembled by PacBio sequencing, DNBSEQ short-read sequencing, and Hi-C sequencing technologies. The final genome size was estimated to be 1.049 Gb, whereas 1.042 Gb of the genome was assigned to 27 pseudochromosomes. The scaffold N50 length was 75.5 Mb with a complete BUSCO score of 97.6%. We identified W and Z chromosomes and validated them by resequencing 14 additional individuals. Totally, 167.04 Mb repetitive elements were identified in the genome, accounting for 15.92% of the total genome size. We predicted 14,935 protein-coding genes, among which 14,931 genes were functionally annotated. This is the most comprehensive and complete de novo assembly of the Pavo genus, and it will serve as a valuable resource for future green peafowl ecology, evolution, and conservation studies.

Prediction of the CYP2D6 enzymatic activity based on investigating of the CYP2D6 genotypes around the vivax malaria patients in Yunnan Province, China.

BACKGROUND: In recent years, the incidence rate of vivax malaria recurrence still had 3.1% in Yunnan Province population after eradication therapy using primaquine (PQ). In order to understand the specific failure reasons for preventing vivax malaria relapses, a preliminary exploration on the CYP2D6 enzyme activity was carried out in the vivax malaria patients in Yunnan Province population by analysing mutational polymorphism in the coding region of CYP2D6 gene. METHODS: Blood samples were collected from vivax malaria patients with suspected relapse (SR) and non-relapsed (NR) malaria in Yunnan Province. The DNA fragments containing 9 exons regions of human CYP2D6 gene were amplified by performing PCR and sequenced. The sequencing results were aligned by using DNAStar 11.0 to obtain the coding DNA sequence (CDS) of CYP2D6 gene. DnaSP 6.11.01 software was used to identify mutant polymorphisms and haplotypes of the CDS chain. The waterfall function of GenVisR package in R was utilized to visualize the mutational landscape. The alleles of CYP2D6 gene were identified according to the criteria prescribed by Human Cytochrome P450 (CYP) Allele Nomenclature Committee Database and the CYP2D6 enzyme activity was predicted based on diploid genotype. RESULTS: A total of 320 maternal CDS chains, including 63 from SR group and 257 from NR group, were obtained. Twelve mutant loci, including c.31 (rs769259), c.100 (rs1065852), c.271 (rs28371703), c.281 (rs28371704), c.294 (rs28371705), c.297 (rs200269944), c.336 (rs1081003), c.408 (rs1058164), c.505 (rs5030865), c.801 (rs28371718), c.886 (rs16947), and c.1,457 (rs1135840) were observed on the 640 CDS chains (including 320 maternal and 320 paternal chains). The high-frequency mutation at rs1135840 (0.703) and low-frequency mutation, such as rs28371703, were detected only in the SR group. The frequency of mutant rs1058164 and rs1135840 were significantly increased in the SR group ([Formula: see text]= 4.468, 5.889, P < 0.05), as opposed to the NR group. Of the 23 haplotypes (from Hap_1 to Hap_23), the nomenclatures of 11 allelic forms could be found: Hap_3 was non-mutant, Hap_2 accounted for the highest frequency (36.9%, 236/640), and Hap_9 had the most complex sequence structure, containing 7 loci mutations. Allele *10 was the most frequent among these genotypes (0.423). Among the allele *10 standard named genotypes, *1/*10, *1/*1 and *2/*10 were significantly more frequent in the NR group ([Formula: see text]= 3.911, P < 0.05) and all showed uncompromised enzyme activity; the impaired genotype *10/*39 was more frequent in the SR group ([Formula: see text]= 10.050, P < 0.05), and genotype *4/*4was detected only in the SR group. CONCLUSION: In the patients receiving PQ dosage in Yunnan Province population, both rs1135840 single nucleotide polymorphism and *10 allele form was common in the CYP2D6 gene. Low-frequency mutation sites, such as rs28371703, were only presented in patients with vivax malaria relapse.

Ten-Year Molecular Surveillance of Drug-Resistant Plasmodium spp. Isolated From the China-Myanmar Border.

Antimalarial drug resistance has emerged as a major threat to global malaria control efforts, particularly in the Greater Mekong Subregion (GMS). In this study, we analyzed the polymorphism and prevalence of molecular markers associated with resistance to first-line antimalarial drugs, such as artemisinin, chloroquine, and pyrimethamine, using blood samples collected from malaria patients in the China-Myanmar border region of the GMS from 2008 to 2017, including 225 cases of Plasmodium falciparum and 194 cases of Plasmodium vivax. In artemisinin resistance, only the C580Y mutation with low frequency was detected in pfk13, and no highly frequent stable mutation was found in pvk12. In chloroquine resistance, the frequency of K76T mutation in pfcrt was always high, and the frequency of double mutations in pvmdr1 of P. vivax has been steadily increasing every year. In pyrimidine resistance, pfdhfr and pvdhfr had relatively more complex mutant types associated with drug resistance sites, and the overall mutation rate was still high. Therefore, artemisinin-based combination therapies are still suitable for use as the first choice of antimalarial strategy in the China-Myanmar border region in the future.

Effects of Sacubitril-Valsartan in Heart Failure With Preserved Ejection Fraction in Patients Undergoing Peritoneal Dialysis.

Aims: The effect of the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril-valsartan in patients with heart failure with preserved ejection fraction (HFpEF) remains unclear, and data on ARNI treatment in peritoneal dialysis (PD) patients are lacking. The present study was designed to assess the efficacy and safety of sacubitril-valsartan in patients with HFpEF undergoing peritoneal dialysis. Methods and Results: End-stage kidney disease (ESKD) patients undergoing PD for 3 months with New York Heart Association (NYHA) class II-IV heart failure, ejection fraction of 50% or higher, and elevated levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) were assigned to receive sacubitril-valsartan. Patients were followed up regularly after medication treatment. The alterations in clinical and biochemical parameters before and after taking sacubitril-valsartan (generally 50-100 mg b.i.d) were investigated, and safety was also assessed. Twenty-one patients were recruited in this study. Compared with baseline levels, NT-proBNP levels [9769.0 (3093.5-21941.0) vs. 3034.0 (1493.2-6503.0), P = 0.002], and heart rate [80.0 (74.5-90.5) vs. 75.0 (70.3-87.0), P = 0.031] were markedly decreased after treatment with sacubitril-valsartan. Signs and symptoms of heart failure (21/21 vs. 15/21, P = 0.021) were obviously alleviated, NYHA classification and E/e' ratio showed a notable trend of improvement after 3-12 months of follow-up. None of the patients showed adverse drug reactions. Conclusions: The present data suggested that sacubitril-valsartan treatment in patients with HFpEF undergoing PD was effective and safe.

Sex-Biased Gene Expression and Evolution in the Cerebrum and Syrinx of Chinese Hwamei (Garrulax canorus).

It is common that males and females display sexual dimorphisms, which usually result from sex-biased gene expression. Chinese hwamei (Garrulax canorus) is a good model for studying sex-biased gene expression because the song between the sexes is quite different. In this study, we analyze cerebrum and syrinx sex-biased gene expression and evolution using the de novo assembled Chinese hwamei transcriptome. In both the cerebrum and syrinx, our study revealed that most female-biased genes were actively expressed in females only, while most male-biased genes were actively expressed in both sexes. In addition, both male- and female-biased genes were enriched on the putative Z chromosome, suggesting the existence of sexually antagonistic genes and the insufficient dosage compensation of the Z-linked genes. We also identified a 9 Mb sex linkage region on the putative 4A chromosome which enriched more than 20% of female-biased genes. Resultantly, male-biased genes in both tissues had significantly higher Ka/Ks and effective number of codons (ENCs) than unbiased genes, and this suggested that male-biased genes which exhibit accelerated divergence may have resulted from positive selection. Taken together, our results initially revealed the reasons for the differences in singing behavior between males and females of Chinese hwamei.