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Qing-wei Zhang,1 Jia-yu Song,2 Jiang-hua Yu,1 Ming-zhen Sun,2 Si-yuan Tang,1 Shao-zhe Yang,1 Lei-jia Cao,1 Hui-fen Wang,1 Li-na Cui,1 Xiu-hong Fu1 1Department of Obstetrics and Gynaecology, Luohe Central Hospital, Luohe, 462000, Henan, China; 2Department of Pharmacology, Luohe Medical College, Luohe, 462000, Henan, China Purpose: In this paper, the association between polymorphisms of IFN-γ+874T/A (rs2430561), IFN-γR1 -56 T/C (rs2234711), IFN-γR1 +95 C/T (rs7749390), and IFN-γR1 -611A/G (rs 1327474) and human papillomavirus (HPV) susceptibility was investigated in rural women from Luohe, Henan, China. Patients and methods: A total of 520 rural women were enrolled from Luohe, including 260 with HPV infection and mild dysplasia or less and 260 without HPV infection. Single-nucleotide polymorphisms (SNPs) of IFN-γ +874T/A, IFN-γR1 -56 T/C, IFN-γR1 +95 C/T and IFN-γR1 -611A/G were genotyped using TaqMan Pre-Designed SNP Genotyping Assays. Serum IFN-γ levels were measured using Human IFN-γ Quantikine ELISA Kit. Multivariate logistic regression analysis was performed to identify the SNPs associated with HPV susceptibility. Serum IFN-γ levels were compared between different genotypes. Results: The polymorphism of IFN-γ +874T/A was associated with HPV susceptibility and +874A carriers had an increased risk. Moreover, the odds ratio was higher in +874 AA carriers than in +874 AT carriers (1.672 vs 2.874). Serum IFN-γ levels were highest in IFN-γ +874 TT carriers, intermediate in AT carriers, and lowest in AA carriers (2.86±1.14 vs 1.57±0.79 vs 0.41±0.22 pg/mL, all P

Objective: To explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it's down-stream mediators in colorectal cancer (CRC) cells., Methods: Quantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues., Results: PZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05)., Conclusion: The mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Adaptive evolution following colonization can affect the impact of invasive species. The fall webworm (FWW) invaded China 40 years ago through a single introduction event involving a severe bottleneck and subsequently diverged into two genetic groups. The well-recorded invasion history of FWW, coupled with a clear pattern of genetic divergence, provides an opportunity to investigate whether there is any sign of adaptive evolution following the invasion. Based on genome-wide SNPs, we identified genetically separated western and eastern groups of FWW and correlated spatial variation in SNPs with geographical and climatic factors. Geographical factors explained a similar proportion of the genetic variation across all populations compared with climatic factors. However, when the two population groups were analysed separately, environmental factors explained more variation than geographical factors. SNP outliers in populations of the western group had relatively stronger response to precipitation than temperature-related variables. Functional annotation of SNP outliers identified genes associated with insect cuticle protein potentially related to desiccation adaptation in the western group and genes associated with lipase biosynthesis potentially related to temperature adaptation in the eastern group. Our study suggests that invasive species may maintain the evolutionary potential to adapt to heterogeneous environments despite a single invasion event. The molecular data suggest that quantitative trait comparisons across environments would be worthwhile., (© 2023 John Wiley & Sons Ltd.)

Tortricidae is one of the largest families in Lepidoptera, including subfamilies of Tortricinae, Olethreutinae, and Chlidanotinae. Here, we assembled the gap-free genome for the subfamily Chlidanotinae using Illumina, Nanopore, and Hi-C sequencing from Polylopha cassiicola, a pest of camphor trees in southern China. The nuclear genome is 302.03 Mb in size, with 36.82% of repeats and 98.4% of BUCSO completeness. The karyotype is 2n = 44 for males. We identified 15412 protein-coding genes, 1052 tRNAs, and 67 rRNAs. We also determined the mitochondrial genome of this species and annotated 13 protein-coding genes, 22 tRNAs, and one rRNA. These high-quality genomes provide valuable information for studying phylogeny, karyotypic evolution, and adaptive evolution of tortricid moths., (© 2024. The Author(s).)

The flower thrips Frankliniella intonsa (Thysanoptera: Thripidae) is a common insect found in flowers of many plants. Sometimes, F. intonsa causes damage to crops through direct feeding and transmission of plant viruses. Here, we assembled a chromosomal level genome of F. intonsa using the Illumina, Oxford Nanopore (ONT), and Hi-C technologies. The assembled genome had a size of 209.09 Mb, with a contig N50 of 997 bp, scaffold N50 of 13.415 Mb, and BUSCO completeness of 92.5%. The assembled contigs were anchored on 15 chromosomes. A set of 14,109 protein-coding genes were annotated in the genome with a BUSCO completeness of 95.0%. The genome contained 491 non-coding RNA and 0.57% of interspersed repeats. This high-quality genome provides a valuable resource for understanding the ecology, genetics, and evolution of F. intonsa, as well as for controlling thrips pests., (© 2024. The Author(s).)

Following invasion, insects can become adapted to conditions experienced in their invasive range, but there are few studies on the speed of adaptation and its genomic basis. Here, we examine a small insect pest, Thrips palmi, following its contemporary range expansion across a sharp climate gradient from the subtropics to temperate areas. We first found a geographically associated population genetic structure and inferred a stepping-stone dispersal pattern in this pest from the open fields of southern China to greenhouse environments of northern regions, with limited gene flow after colonization. In common garden experiments, both the field and greenhouse groups exhibited clinal patterns in thermal tolerance as measured by critical thermal maximum (CTmax) closely linked with latitude and temperature variables. A selection experiment reinforced the evolutionary potential of CTmax with an estimated h2 of 6.8% for the trait. We identified 3 inversions in the genome that were closely associated with CTmax, accounting for 49.9%, 19.6%, and 8.6% of the variance in CTmax among populations. Other genomic variations in CTmax outside the inversion region were specific to certain populations but functionally conserved. These findings highlight rapid adaptation to CTmax in both open field and greenhouse populations and reiterate the importance of inversions behaving as large-effect alleles in climate adaptation., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

The Japanese sawyer beetle Monochamus alternatus (Coleoptera: Cerambycidae) is a pest in pine forests and acts as a vector for the pine wood nematode Bursaphelenchus xylophilus, which causes the pine wilt disease. We assembled a high-quality genome of M. alternatus at the chromosomal level using Illumina, Nanopore, and Hi-C sequencing technologies. The assembled genome is 767.12 Mb, with a scaffold N50 of 82.0 Mb. All contigs were assembled into ten pseudo-chromosomes. The genome contains 63.95% repeat sequences. We identify 16, 284 protein-coding genes in the genome, of which 11,244 were functionally annotated. The high-quality genome of M. alternatus provides an invaluable resource for the biological, ecological, and genetic study of this beetle and opens new avenues for understanding the transmission of pine wood nematode by insect vectors., (© 2024. The Author(s).)

Modern Bai Jiu(liquor) was called Shao Jiu in ancient times.By consulting ancient books, it was found that there was a distillation and preparation process of Shao Jiu before the Ming Dynasty, but due to its high toxicity, the scope of application was limited, and there were few records of its medicinal use.However many records of its medicinal use was found in the Compendium of Materia Medica («»).By comparing the medical books that recorded Shao Jiu in previous dynasties, it is found that the Compendium of Materia Medica comprehensively records the relevant cognition and application of the medicinal use of Shao Jiu for the first time. The book lists in detail the causes of the toxicity of Shao Jiu and the methods to avoid it, comprehensively expounds its characteristics, efficacy and indications, lists a variety of ways to use it, skillfully uses Shao Jiu to treat syphilis sores, and proposes that high-concentration Shao Jiu can be used as a solvent for medical liquor.The record of Shao Jiu in the Compendium of Materia Medica had a profound impact on the medical liquor of later generations.The use of Shao Jiu in the Qing Dynasty continued to expand, and the types of medicinal liquor were also constantly enriched. The record of Shao Jiu in the Compendium of Materia Medica can also provide a reference for the medicinal use of modern liquor.

Objective: Iron accumulation is associated with osteoporosis. This study aims to explore the effect of chronic iron accumulation induced by hepcidin1 deficiency on aging osteoporosis., Methods: Iron accumulation in hepcidin1 knockout aging mice was assessed by atomic absorption spectroscopy and Perl's staining. Bone microarchitecture was observed using Micro-CT. Hepcidin, ferritin, oxidative stress, and markers of bone turnover in serum were detected by enzyme-linked immunosorbent assay. Bone formation and resorption markers were measured by real-time quantitative PCR. Cell aging was induced by D-galactose treatment. CCK-8, flow cytometry, EdU assays, and Alizarin red staining were performed to reveal the role of hepcidin1 knockout in cell model. Iron Colorimetric Assay Kit and western blot were applied to detect iron and ferritin levels in cells, respectively., Results: In hepcidin1-knockout mice, the ferritin and iron contents in liver and tibia were significantly increased. Iron accumulation induced by hepcidin1 knockout caused a phenotype of low bone mass and deteriorated bone microarchitecture. Osteogenic marker was decreased and osteoclast marker was increased in mice, accompanied by increased oxidative stress level. The mRNA expression levels of osteoclast differentiation markers (RANKL, Mmp9, OPG, Trap, and CTSK) were up-regulated, while bone formation markers (OCN, ALP, Runx2, SP7, and Col-1) were down-regulated in model group, compared to wild type mice. In vitro, hepcidin1 knockdown inhibited proliferation and osteogenic differentiation, while promoted apoptosis, with increased levels of iron and ferritin., Conclusion: Iron accumulation induced by hepcidin1 deficiency aggravates the progression of aging osteoporosis via inhibiting osteogenesis and promoting osteoclast genesis., (© 2024. The Author(s).)

The fruit fly Zeugodacus tau (Diptera: Tephritidae) is a major pest of melons and other cucurbits in Southeast Asia. In this study, we used Illumina, Nanopore, and Hi-C sequencing technologies to assemble a reference genome of Z. tau at the chromosomal level. The assembled genome was 421.79 Mb and consisted of six chromosomes (one X-chromosome + five autosomes). The contig N50 was 4.23 Mb. We identified 20,922 protein-coding genes, of which 17,251 (82.45%) were functionally annotated. Additionally, we found 247 rRNAs, 435 tRNAs, 67 small nuclear RNAs, and 829 small RNAs in the genome. Repetitive elements accounted for 55.30 Mb (13.15%) of the genome. This high-quality genome assembly is valuable for evolutionary and genetic studies of Z. tau and its relative species., (© 2023. The Author(s).)

Background: Several agricultural fungicides are known to affect insect pests directly and these effects may be transgenerational and mediated through impacts on endosymbionts, providing opportunities for pest control. The cotton aphid Aphis gossypii is a polyphagous pest that can cause large crop yield losses. Here, we tested the effects of three fungicides, pyraclostrobin, trifloxystrobin and chlorothalonil, on the fitness and Buchnera endosymbiont of A. gossypii., Results: The formulations of trifloxystrobin and pyraclostrobin, and the active ingredient of pyraclostrobin produced dose-dependent mortality in A. gossypii, whereas there was no dose-dependent mortality for chlorothalonil. The formulations of trifloxystrobin and pyraclostrobin significantly reduced the lifespan and fecundity of A. gossypii, and increased the density of Buchnera in the parental generation but not the (unexposed) F 1 . When the active ingredient of pyraclostrobin was tested, the lifespan of the F 0 generation was also reduced, but the density of Buchnera was not, indicating that non-insecticidal chemicals in the fungicide formulation may affect the density of the endosymbiont of A. gossypii. There was no transgenerational effect of the active ingredient of pyraclostrobin on the lifespan and Buchnera of (unexposed) F 1 ., Conclusions: Our results suggest that formulations of two strobilurin fungicides have immediate impacts on the fitness of A. gossypii, and chemicals in the formulation impact the density of the primary Buchnera endosymbiont. Our study highlights the potential effects of non-insecticidal chemicals of fungicides on aphid pests and their primary endosymbionts but direct connections between fitness and Buchnera densities remain unclear. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Objective: To investigate the clinical phenotype and gene mutation characteristics of MYH9-related disorder (MYH9-RD). Methods: The clinical data of 66 patients with MYH9-RD in the First Affiliated Hospital of Soochow University from January 2010 to December 2022 were retrospectively analyzed. According to the bleeding symptom, the patients were divided into bleeding and non-bleeding group, and according to the mutation sites, the patients were divided into non-muscle myosin heavy chain ⅡA head region (MD) and tail region (TD) mutation group. Statistical analysis was made to explore the clinical features in different groups such as platelet counts, bleeding, renal function, cataracts and hearing as well as MYH9 gene mutations. Results: A total of 66 MYH9-RD patients were included, with 28 males and 38 females, diagnosis age of 1-63(26±2) years. And 41% (27/66) of the patients had no family history. All patients presented with macrothrombocytopenia and normal platelet aggregation(10/10), 92% (54/59) of the patients had visible blue inclusion bodies in neutrophils, 30% (20/66) had bleeding symptoms, 45% (22/49) had proteinuria or glomerulonephropathy, 20% (8/41) had bilateral hearing impairment, and 10% (4/42) had bilateral cataracts. 18 mutation sites were identified in total, including 15 missense, 1 splicing and 2 termination mutations. Among them, p.Asp1424Asn, p.Arg1933* and p.Arg702His/Cys mutations were identified in 56% (29/52) of the patients, and p.Ser96Leu, Arg1165Cys and p.Glu1841Lys mutations were recurrent mutations, while p.Ala44Thr, p.Asp1447Ala and c.3838-2A>G mutations were novel mutations. The average platelet count of patients in bleeding group was (19±3)×10 9 /L, which was significantly less than (36±3)×10 9 /L in non-bleeding group ( P <0.001). Compared with TD mutation group, patients of MD mutation group were presented with lower platelet count and higher risk of bleeding, as well as more severe clinical presentations including renal and hearing impairment and cataracts (all P <0.05). Conclusion: Mutations of p.Asp1424Asn, p.Arg1933* and p.Arg702His/Cys in MYH9 gene are hotspot mutations for MYH9-RD patients, Compared with TD mutation group, patients of MD mutation group were presented with lower platelet count and higher risk of bleeding, as well as more severe clinical presentations including renal and hearing impairment and cataracts.

Rebalance of coagulation and anticoagulation to achieve a hemostatic effect has recently gained attention as an alternative therapeutic strategy for hemophilia. We engineered a humanized chimeric antibody, SR604, based on a previously published murine antibody, HAPC1573, which selectively blocks the anticoagulant activity of human activated protein C (APC). SR604 effectively blocked the anticoagulation activities of APC in human plasma deficient in various coagulation factors in vitro with affinities ∼60 times greater than that of HAPC1573. SR604 exhibited prophylactic and therapeutic efficacy in the tail-bleeding and knee-injury models of hemophilia A and B mice expressing human APC (humanized hemophilic mice). SR604 did not interfere with the cytoprotection and endothelial barrier function of APC, nor were there obvious toxicity effects in humanized hemophilic mice. Pharmacokinetic study showed a high bioavailability (106%) of subcutaneously injected SR604 in cynomolgus monkeys. These results demonstrate that SR604 is expected to be a safe and effective therapeutic and/or prophylactic agent with a prolonged half-life for patients with congenital factor deficiencies including hemophilia A and B., (© 2023 by The American Society of Hematology.)

Background: Field control of pest thrips mainly relies on insecticides, but the toxicity of insecticides can vary among thrips species and populations. In this study, we examined the susceptibility of multiple field populations of two thrips pests, Frankliniella occidentalis, and Thrips palmi, that often co-occur on vegetables, to nine insecticides belonging to seven subgroups., Results: The highest level of variation in susceptibility among F. occidentalis populations was for spinetoram (73.92 fold difference between most resistant and most susceptible population), followed by three neonicotinoids (8.06-15.99 fold), while among T. palmi populations, it was also for spinetoram (257.19 fold), followed by emamectin benzoate, sulfoxaflor, and acetamiprid (23.64-45.50 fold). These findings suggest evolved resistance to these insecticides in some populations of the two thrips. One population of F. occidentalis had a particularly high level of resistance overall, being the most resistant for five of the nine insecticides tested. Likewise, a population of T. palmi had high resistance to all nine insecticides, again suggesting the evolution of resistance to multiple chemicals. For F. occidentalis, the LC 95 values of most populations were higher than the field-recommended dosage for all insecticides except chlorfenapyr and emamectin benzoate. For several T. palmi populations, the LC 95 values also tended to be higher than recommended dosages, except in the case of emamectin benzoate and spinetoram., Conclusions: Our study found interspecific and intraspecific variations in the susceptibility of two thrips to nine insecticides and multiple resistance in some populations, highlighting the need for ongoing monitoring and resistance management. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Objectives: Depression is an increasingly serious mental health problem worldwide. Therefore, this study aimed to explore the association between chronic disease and depression and to further test the moderating role of social participation in this association., Study Design: This is a cross-sectional study., Methods: We screened 6421 subjects from the 2018 wave of the China Health and Retirement Longitudinal Study database. Social participation and depressive symptoms were assessed using the 12-item self-made scale and 10-item Center for Epidemiological Studies Depression Scale, respectively. Hierarchical regression was used to determine the main effect of chronic disease and depression and the moderating effect of social participation on the relationship between chronic disease and depression., Results: In this study, 3172 (49.40%) eligible participants were male, 4680 (72.90%) older adults were concentrated in the 65-74 years group, and 68.20% reported good health status. In addition, gender, area, education level, marital status, health status, health insurance, health service utilization, and physical activity intensity were significant factors associated with participants' depression status (P < 0.05). The results also showed that a higher number of chronic diseases were associated with a higher depression score after adjusting for confounders (single disease: β = 0.074, P < 0.001; multimorbidity: β = 0.171, P < 0.001) and that social participation played a moderating role in this association (β = -0.030, P < 0.05)., Conclusions: This study tentatively suggests that a higher number of chronic diseases are associated with rising depression scores in the older Chinese population. In addition, the moderating effect of social participation suggests that more active social engagement should be promoted in this population to alleviate the depressive mood., (Copyright © 2023 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: Hemoporfin-mediated photodynamic therapy (PDT) is an effective treatment for port-wine stains (PWS), and pain is the main adverse effect of this therapy. General anesthesia is commonly used for pain management during PDT, but the effect of general anesthetics on the subsequent treatment efficacy of PDT in PWS has not been reported., Objectives: To assess the use of general anesthesia combined with PDT compared with PDT alone in 207 PWS patients, and to provide further safety and efficacy data on this combined therapy., Methods: Propensity score matching (PSM) was used at a 2:1 ratio to create a general anesthetic group ( n  = 138) and a highly comparable nonanesthetic group ( n  = 69). The clinical outcomes were evaluated, and the treatment reactions and adverse effects were recorded after one treatment with PDT., Results: After matching, there was no significant difference in the demographic data of the patients in the two groups ( p  > 0.05), while the treatment efficacy was significantly higher in the general anesthetic group than in the nonanesthetic group (76.81 vs. 56.52%, p  < 0.05). Moreover, logistic regression analysis confirmed that patients receiving general anesthesia showed an association with a good response to PDT (OR = 3.06; 95% CI, 1.57-6.00; p  = 0.0011). Purpura lasted longer in the general anesthetic group, but the other treatment reactions and adverse effects were similar in the two groups ( p  > 0.05). No serious systemic adverse reactions were observed., Conclusion: We recommend this combined therapy, which is associated with painless, as a high efficacy treatment option for PWS patients, especially for patients with a poor response to multiple PDT alone treatments., 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 © 2023 Hu, Chen, Wang, Wang, Chen, Cao, Jiang, Wang, Qian, Chen, Chen and Li.)

Background: The two-spotted spider mite (TSSM), Tetranychus urticae (Acari: Tetranychidae), is a cosmopolitan phytophagous pest in agriculture and horticulture. It has developed resistance to many acaricides by target-site mutations. Understanding the status and evolution of resistant mutations in the field is essential for resistance management. Here, we applied a high-throughput Kompetitive allele-specific polymerase chain reaction (KASP) method for detecting six mutations conferring resistance to four acaricides of the TSSM. We genotyped 3274 female adults of TSSM from 43 populations collected across China in 2017, 2020, and 2021., Results: The KASP genotyping of 24 testing individuals showed 99% agreement with Sanger sequencing results. KASP assays showed that most populations had a high frequency of mutations conferring avermectin (G314D and G326E) and pyridaben (H92R) resistance. The frequency of mutation conferring bifenazate (A269V and G126S) and etoxazole (I1017F) resistance was relatively low. Multiple mutations were common in the TSSM, with 70.2% and 24.6% of individuals having 2-6 and 7-10 of 10 possible resistant alleles, respectively. No loci were linked in most populations among the six mutations, indicating the development of multiple resistance is mainly by independent selection. However, G314D and I1017F on the nuclear genome deviated from Hardy-Weinberg equilibrium in most populations, indicating significant selective pressure on TSSM populations by acaricides or fitness cost of the mutations in the absence of acaricide selection., Conclusion: Our study revealed that the high frequency of TSSMs evolved multiple resistant mutations in population and individual levels by independent selection across China, alarming for managing multiple-acaricides resistance. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Background: Pesticide resistance is a long-standing and growing problem in the chemical control of invertebrate pests. Molecular diagnostic methods can facilitate pesticide resistance management by accurately and efficiently detecting resistant mutations and their frequency. In this study, the kompetitive allele specific PCR (KASP) approach, a technology for high-throughput single nucleotide polymorphism (SNP) genotyping, is validated as a useful method for characterizing genotypes at a pesticide-resistance locus for the first time. We focus on the spinetoram resistance mutation of G275E in the nicotinic acetylcholine receptor alpha 6 (nAChR α6) subunit gene of Thrips palmi., Results: Of the 341 individuals of Thrips palmi tested, 98.24% were successfully genotyped, with 100% concordance with Sanger sequencing results. We then quantitatively mixed genomic DNA of known genotypes to establish 21 DNA mixtures with a resistant allele frequency ranging from 0 to 100% at steps of 5%. The linear discriminant analysis (LDA) showed that 75.8% of original grouped cases were correctly classified; six groups had no overlap in membership (resistant allele frequency: 0%, 5%, 10-75%, 80-85%, 90-95%, and 100%). When we chose 11 pooled samples with 10% steps for LDA, 84.4% of original grouped cases were correctly classified; seven groups had no overlap in membership (0%, 10%, 20-30%, 40-70%, 80%, 90%, 100%). The results indicated that KASP applied to pooled samples may provide a semi-quantitative estimate of resistance., Conclusions: Our study points to the suitability of KASP for high-throughput genotyping of genotypes affecting pesticide resistance and semi-quantitative assessments of resistance allele frequencies in populations. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Prostate cancer is one of the most lethal malignancies, and androgen deprivation therapy remains the mainstay of treatment for prostate cancer patients. Although androgen deprivation can initially come to remission, the disease often develops into castration-resistant prostate cancer (CRPC), which is still dependent on androgen receptor (AR) signaling and is related to a poor prognosis. Some success against CRPC has been achieved by drugs that target AR signaling, but secondary resistance uninterrupted emerges, and new therapies are urgently needed. In this study, we identified a potent small molecule compound, ZY-444, that suppressed PCa cells proliferation and metastasis, and inhibited tumor growth both in subcutaneous. Transcriptome sequencing analysis showed that TNFAIP3 was significantly elevated in prostate cancer cells after ZY-444 treatment. Further studies through overexpression of TNFAIP3 confirmed that TNFAIP3, as a direct target gene of ZY-444, contributes to the functions of ZY-444. In addition, we demonstrated the effects of TNFAIP3 on prostate cancer cell apoptosis, migration and proliferation to elucidate the mechanism of ZY-444. We found that TNFAIP3 inhibited the TNF signaling pathway, which could inhibit cell migration and proliferation and contribute to apoptosis. Overall, these findings highlighted TNFAIP3 as a tumor suppressor gene in the regulation of the progression and metastatic potential of prostate cancer and that targeting TNFAIP3 by ZY-444 might be a promising strategy for prostate cancer treatment., Competing Interests: None., (AJCR Copyright © 2023.)

In this study, an overview of systematic reviews/Meta-analysis(SR/MA) of Chinese herbal injections for sepsis was performed to provide references for clinical practice and promote the quality improvement of clinical evidence. Eight Chinese and English databases such as CNKI, Medline, and EMbase were electronically searched for SR/MA of Chinese herbal injections for sepsis from database inception to June 2022. AMSTAR 2, PRISMA 2020, and GRADE system, combined with Recommendations for Clinical Evidence Grading on Traditional Chinese Medicine Based on Evidence Body, were applied to evaluate the methodological quality, reporting quality, and evidence quality of the included articles. Twenty-seven articles of SR/MA were included, containing four Chinese herbal injections(Xuebijing Injection, Shenfu Injection, Shenmai Injection, and Shengmai Injection). AMSTAR 2 checklist showed that the methodological quality of the SR/MA ranged from moderate to very low. Item 2(prior study design) was the critical item with poor scores, and the non-critical items with poor scores were items 3(explain the selection of the study designs), items 10(report on the sources of funding), and items 16(conflicts of interest stated). In terms of PRISMA 2020, items in eight topics with complete reporting of missing&gt;50%, including search strategy, certainty assessment, results of syntheses, certainty of evidence, registration and protocol, support, competing interests, availability of data, code and other materials. The included SR/MA involved 30 outcome indicators. Evidence quality of mortality, APACHE Ⅱ, and safety, the top three outcome indicators, was evaluated, and all of them were graded as the medium level. The lack of random allocation sequence, allocation concealment mechanism, blinding, and trial sample size was the main reason for the reduction of the evidence level. The available evidence shows that Chinese herbal injections can serve as an effective and safe adjunctive treatment for sepsis, which can reduce mortality, inhibit inflammation, improve coagulation function, and regulate immune function, tissue perfusion, and oxygenation in patients with sepsis. However, the quality of SR/MA was suboptimal, and more high-quality SR/MA is needed to provide evidence to support the efficacy and safety of Chinese herbal injections in the treatment of sepsis.

Microbiota has recently emerged as a critical factor associated with multiple malignancies. Nasopharyngeal carcinoma (NPC) is highly associated with Epstein-Barr virus (EBV); the oncovirus resides and is transmitted in the oral cavity. However, the alternation of oral microbiota in NPC patients and its potential link to EBV reactivation and host cell response under the simultaneous existence of EBV and specific bacteria is largely unknown. Here, oral microbiota profiles of 303 NPC patients and controls with detailed clinical information, including serum EBV anti-virus capsid antigen (VCA) IgA level, were conducted. A distinct microbial community with lower diversity and imbalanced composition in NPC patients was observed. Notably, among enriched bacteria in patients, Streptococcus sanguinis was associated with anti-VCA IgA, an indicator of NPC risk and EBV reactivation. By measuring the concentration of its metabolite, hydrogen peroxide (H 2 O 2 ), in the saliva of clinical patients, we found the detection rate of H 2 O 2 was 2-fold increased compared to healthy controls. Further coculture assay of EBV-positive Akata cells with bacteria in vitro showed that S. sanguinis induced EBV lytic activation by its metabolite, H 2 O 2 . Host and EBV whole genome-wide transcriptome sequencing and EBV methylation assays showed that H 2 O 2 triggered the host cell signaling pathways, notably tumor necrosis factor alpha (TNF-α) via NF-κB, and induced the demethylation of the global EBV genome and the expression of EBV lytic-associated genes, which could result in an increase of virus particle release and potential favorable events toward tumorigenesis. In brief, our study identified a characterized oral microbial profile in NPC patients and established a robust link between specific oral microbial alteration and switch of latency to lytic EBV infection status in the oral cavity, which provides novel insights into EBV's productive cycle and might help to further clarify the etiology of NPC. IMPORTANCE EBV is classified as the group I human carcinogen and is associated with multiple cancers, including NPC. The interplays between the microbiota and oncovirus in cancer development remain largely unknown. In this study, we investigate the interactions between resident microbes and EBV coexistence in the oral cavity of NPC patients. We identify a distinct oral microbial feature for NPC patients. Among NPC-enriched bacteria, we illustrated that a specific species, S. sanguinis, associated with elevated anti-IgA VCA in patients, induced EBV lytic activation by its by-product, H 2 O 2 , and activated the TNF-α/NF-κB pathway of EBV-positive B cells in vitro , together with increased detection rate of H 2 O 2 in patients' oral cavities, which strengthened the evidence of bacteria-virus-host interaction in physiological circumstances. The effects of imbalanced microbiota on the EBV latent-to-lytic switch in the oral cavity might create the likelihood of EBV infection in epithelial cells at the nasopharynx and help malignant transition and cancer development.

Various biomarkers targeting cell-free DNA (cfDNA) and circulating proteins have been tested for pan-cancer detection. Oncofetal chondroitin sulfate (ofCS), which distinctively modifies proteoglycans (PGs) of most cancer cells and binds specifically to the recombinant Plasmodium falciparum VAR2CSA proteins (rVAR2), is explored for its potential as a plasma biomarker in pan-cancer detection. To quantitate the plasma ofCS/ofCSPGs, we optimized an ELISA using different capture/detection pairs (rVAR2/anti-CD44, -SDC1, and -CSPG4) in a case-control study with six cancer types. We show that the plasma levels of ofCS/ofCSPGs are significantly higher in cancer patients (P values, 1.2 × 10 -2 to 4.4 × 10 -10 ). Validation studies are performed with two independent cohorts covering 11 malignant tumors. The individuals in the top decile of ofCS-CD44 have more than 27-fold cancer risk (OR = 27.8, 95%CI = 18.8-41.4, P = 2.72 × 10 -62 ) compared with the lowest 20%. Moreover, the elevated plasma ofCS-CD44 could be detected at the early stage of pan-cancer with strong dose-dependent odds risk prediction., (© 2023. The Author(s).)

Background: The diamondback moth (DBM) Plutella xylostella has developed resistance to almost all insecticides used to control it. Populations of DBM in temperate regions mainly migrate from annual breeding areas. However, the distribution pattern of insecticide resistance of DBM within the context of long-distance migration remains unclear., Results: In this study, we examined the frequency of 14 resistance mutations for 52 populations of DBM collected in 2010, 2011, 2017 and 2018 across China using a high-throughput KASP genotyping method. Mutations L1041F and T929I conferring pyrethroid resistance, and mutations G4946E and E1338D conferring chlorantraniliprole resistance were near fixation in most populations, whereas resistant alleles of F1020S, M918I, A309V and F1845Y were uncommon or absent in most populations. Resistance allele frequencies were relatively stable among different years, although the frequency of two mutations decreased. Principal component analysis based on resistant allele frequencies separated a southern population as an outlier, whereas the immigrants clustered with other populations, congruent with the migration pattern of northern immigrants coming from the Sichuan area of southwestern China. Most resistant mutations deviated from Hardy-Weinberg equilibrium due to a lower than expected frequency of heterozygotes. The deviation index of heterozygosity for resistant alleles was significantly higher than the index obtained from single nucleotide polymorphisms across the genome. These findings suggest heterogeneous selection pressures on resistant mutations., Conclusion: Our results provide a picture of resistant mutation patterns in DBM shaped by insecticide usage and migration of this pest, and highlight the widespread distribution of resistance alleles in DBM. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Objective: To report the clinical manifestations and laboratory features of five patients with congenital thrombotic thrombocytopenic purpura (cTTP) and explore its standardized clinical diagnosis and treatment along with a review of literature. Methods: Clinical data of patients, such as age of onset, disease manifestation, personal history, family history, and misdiagnosed disease, were collected. Treatment outcomes, therapeutic effects of plasma infusion, and organ function evaluation were observed. The relationship among the clinical manifestations, treatment outcomes, and ADAMTS13 gene mutation of patients with cTTP was analyzed. Additionally, detection of ADAMTS13 activity and analysis of ADAMTS13 gene mutation were explored. Results: The age of onset of cTTP was either in childhood or adulthood except in one case, which was at the age of 1. The primary manifestations were obvious thrombocytopenia, anemia, and different degrees of nervous system involvement. Most of the patients were initially suspected of having immune thrombocytopenia. Acute cTTP was induced by pregnancy and infection in two and one case, respectively. ADAMTS13 gene mutation was detected in all cases, and there was an inherent relationship between the mutation site, clinical manifestations, and degree of organ injury. Therapeutic or prophylactic plasma transfusion was effective for treating cTTP. Conclusions: The clinical manifestations of cTTP vary among individuals, resulting in frequent misdiagnosis that delays treatment. ADAMTS13 activity detection in plasma and ADAMTS13 gene mutation analysis are important bases to diagnose cTTP. Prophylactic plasma transfusion is vital to prevent the onset of the disease.

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

AbstractThe movement of individuals through continuous space is typically constrained by dispersal ability and dispersal barriers. A range of approaches have been developed to investigate these. Kindisperse is a new approach that infers recent intergenerational dispersal (σ) from close kin dyads and appears particularly useful for investigating taxa that are difficult to observe individually. This study, focusing on the mosquito Aedes aegypti , shows how the same close kin data can also be used for barrier detection. We empirically demonstrate this new extension of the method using genome-wide sequence data from 266 Ae. aegypti . First, we use the spatial distribution of full-sib dyads collected within one generation to infer past movements of ovipositing female mosquitoes. These dyads indicated the relative barrier strengths of two roads and performed favorably against alternative genetic methods for detecting barriers. We then use Kindisperse to quantify recent intergenerational dispersal ( σ = 81.5 -197.1 m generation -1/2 ) from the difference in variance between the sib and the first cousin spatial distributions and, from this, estimate effective population density ( ρ = 833 -4,864 km -2 ). Dispersal estimates showed general agreement with those from mark-release-recapture studies. Barriers, σ, ρ, and neighborhood size (331-526) can inform forthcoming releases of dengue-suppressing Wolbachia bacteria into this mosquito population.

Background: Thrips pests cause increasing damage to crops around the world. Widespread usage of some insecticides against thrips has now led to the evolution of resistance to several active ingredients, and new insecticides are required. This study examined the toxicity of the novel insecticide broflanilide to multiple populations of several thrips pests., Results: Bioassays showed that thrips populations had LC 50 values ranging from 0.5 to almost 300 mg·L -1 . A population of Frankliniella occidentalis had the highest LC 50 value at 290.63 mg·L -1 , while a population of Echinothrips americanus had the lowest LC 50 value at 0.51 mg L -1 . LC 50 values among seven populations of Thrips palmi ranged from 2.5689 to 23.6754 mg·L -1 , indicating intraspecific variation in toxicity. In this species, the toxicity of broflanilide was relatively higher in adults than in larvae. More than 90% of eggs of T. palmi could not develop into larvae when treated with 5-50 mg L -1 broflanilide. Compared to five commonly used insecticides, broflanilide showed relatively high toxicity to T. palmi. Field control tests with T. palmi showed that control efficacy (from 90.44% to 93.14%) was maintained from day three to day 14 after treatment with 22.5 and 45 ga.i hm -1 broflanilide., Conclusion: Broflanilide is potentially a useful insecticide for controlling Thrips hawaiiensis, Frankliniella intonsa, Megalurothrips usitatus. E. americanus, and some populations of T. palmi. However, the variation in toxicity of this insecticide to different species, populations, and developmental stages indicates that target species and life stages may need to be carefully considered. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

The North China Medical College typically represented medical colleges for traditional Chinese medicine in the 1930s when many of them were set up. It was based on the principles of centring on traditional Chinese medicine, following western medicine and integrated medicine in teaching. This led to the emergence of a great number of people with a high level of traditional Chinese medicine and strong belief in it. In terms of the textbooks and handouts for western medicine, compared to similar textbooks in other medical colleges, such as the Medical College of Xie He, at that time, the textbooks in the North China Medical College covered a variety of perspectives and categories. It was found that 20 textbooks for western medicine in the North China Medical College were designed reasonably in content and were simple and applicable in teaching. More importantly, it contained some traditional Chinese medicine in different degrees, with its typical characteristics. The course design and textbook compilation provided references for the teaching in contemporary medical universities.

Background: It remains controversial who would benefit from adjuvant chemotherapy (ACT) in patients with early-stage non-small cell lung cancer (NSCLC). We aim to construct a polygenic hazard score (PHS) to predict prognosis and ACT benefit among NSCLC patients., Methods: We conducted a retrospective study including 1,395 stage I-II NSCLC patients. We performed a genome-wide association study (GWAS) on overall survival (OS) in patients treated with ACT (SYSUCC ACT set, n=404), and then developed a PHS using LASSO Cox regression in a random subset (training, n=202) and tested it in the remaining set (test, n=202). The PHS was further validated in two independent datasets (SYSUCC surgery set, n=624; PLCO cohort, n=367)., Results: The GWAS-derived PHS consisting of 37 single-nucleotide polymorphisms (SNPs) was constructed to classify patients into high and low PHS groups. For patients treated with ACT, those with low PHS had better clinical outcomes than high PHS (test set: HR =0.21, P<0.001; PLCO ACT set: HR =0.33, P=0.260). Similar results were found in the extended validation cohorts including patients with or without ACT (SYSUCC: HR =0.48, P<0.001; PLCO: HR =0.60, P=0.033). Within subgroup analysis by treatment or clinical factors, we further observed consistent results for the prognostic value of the PHS. Notably, ACT significantly improved OS in stage II patients with low PHS (HR =0.26, P<0.001), while there was no ACT survival benefit among patients with high PHS (HR =0.97, P=0.860)., Conclusions: The PHS improved prognostic stratification and could help identify patients who were most likely to benefit from ACT in early-stage NSCLC., Competing Interests: Conflicts of Interest:All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-139/coif). The authors have no conflicts of interest to declare., (2022 Translational Lung Cancer Research. All rights reserved.)

Gastritis is a common inflammation of stomach with multiple pathogenesis. This study was designed to investigate the protective effects of oral octreotide (OCT) against ethanol-induced acute gastric injury and H. pylori-induced chronic gastritis via promoting gastric mucosa restoration, reducing gastric acid secretion and inflammation. Male C57BL/6J mice were randomly divided and treated with three doses of OCT (0.5, 2.5, 10 mg/kg) alone or combined respectively with 10 mg/kg omeprazole (OME), 0.2 g/L metronidazole (MTZ)/0.1 g/L clarithromycin (CLR) in drinking water. Oxidative stress analysis, bacterial load analysis, qPCR, gastric histopathology examinations were performed in our study. Ethanol-induced acute gastric ulcer was restored by OCT alone at doses of 2.5 mg/kg, or combined with OME as indicated by markedly reducing Gastrin, Il-6 and Il1b expression through induction of Muc5ac and Occludin, significantly improving hyperacidity and gastric bleeding. As well, OCT combined with MTZ/CLR restored the integrity of gastric mucosa damaged by H. pylori via elevating the expression of Muc5ac and somatostatin receptor 2, decreasing inflammation and increasing the number of chorionic or glands. Besides, OCT is more suitable for long-term medication in the treatment of chronic gastritis than OME. In conclusion, our results proved that the newly developed oral OCT-based therapies were more effective to reverse gastric mucosa damage and inflammation in ethanol and H. pylori infection-induced gastric injury, it is of great significance for supplementing new clinical regimens for the treatment of acute and chronic gastritis., (Copyright © 2022. Published by Elsevier B.V.)

Farnesoid X receptor (FXR), a member of the nuclear receptor superfamily, is a vital ligand-activated transcriptional factor, which is highly expressed in the liver, intestine, and adrenal gland. However, FXR homeostasis is influenced by many factors, such as diet and circadian rhythm, and the expression of FXR differs in diverse organs. Currently, there is no method to monitor the FXR homeostasis in real time, which restricts us from further investigating the function of FXR under physiological and pathological conditions. In this project, classic FXR agonists were selected to be modified to targeting FXR. The photo-cross-linking diazirine group and alkynyl, a click reaction group, were incorporated to the ligands. Through biorthogonal reaction, fluorophore was linked to the ligands to realize the monitoring of FXR expression in cells.

Background: Tuberculosis (TB) is a chronic infectious disease caused by the Mycobacterium tuberculosis complex (MTBC), which is the leading cause of death from infectious diseases. The rapid and accurate microbiological detection of the MTBC is crucial for the diagnosis and treatment of TB. Metagenomic next-generation sequencing (mNGS) has been shown to be a promising and satisfying application of detection in infectious diseases. However, relevant research about the difference in MTBC detection by mNGS between bronchoalveolar lavage fluid (BALF) and lung biopsy tissue specimens remains scarce., Methods: We used mNGS to detect pathogens in BALF and lung biopsy tissue obtained by CT-guide percutaneous lung puncture (CPLP) or radial endobronchial ultrasound transbronchial lung biopsy (R-EBUS-TBLB) from 443 hospitalized patients in mainland China suspected of pulmonary infections between May 1, 2019 and October 31, 2021. Aim to evaluate the diagnostic performance of mNGS for detecting MTBC and explore differences in the microbial composition in the 2 specimen types., Results: Among the 443 patients, 46 patients finally were diagnosed with TB, of which 36 patients were detected as MTBC positive by mNGS (8.93%). Striking differences were noticed in the higher detection efficiency of lung biopsy tissue compared with BALF (P = 0.004). There were no significant differences between the 2 specimen types in the relative abundance among the 27 pathogens detected by mNGS from the 36 patients., Conclusions: This study demonstrates that mNGS could offer an effective detection method of MTBC in BALF or lung tissue biopsy samples in patients suspected of TB infections. When it comes to the situations that BALF samples have limited value to catch pathogens for special lesion sites or the patients have contraindications to bronchoalveolar lavage (BAL) procedures, lung biopsy tissue is an optional specimen for MTBC detection by mNGS. However, whether lung tissue-mNGS is superior to BALF-mNGS in patients with MTBC infection requires further prospective multicenter randomized controlled studies with more cases., (© 2022. The Author(s).)

Objectives: To establish the ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to detect ethanol metabolites phosphatidylethanol (PEth) in whole blood., Methods: An appropriate amount of aqueous solution including 1% formic acid was added to 100 μL whole blood, the protein was precipitated with acetone, centrifuged and the supernatant was purified and enriched by using Bond Elut Certify column. The eluent was redissolved with 1/1 isopropanol/acetonitrile ( v / v ) solution after nitrogen blowing and then tested by UPLC-MS/MS. Selective reaction monitoring scanning was carried out in negative ionization mode, and quantitative analysis was performed by external standard method., Results: PEth showed a linear relationship over the concentration range of 1-160 ng/mL in whole blood ( r =0.999 9) with peak area. The detection limit was 0.2 ng/mL, the quantification limit was 1 ng/mL, the recovery rate was 97.43%-103.61%, the accuracy was 0.99%-1.77%, the intra-day precision was 0.4%-2.4%, and the inter-day precision was 1.1%-3.3%, and the matrix effect was 91.00%-99.55%. PEth was not detected in the in vitro blood samples supplemented with ethanol. PEth was detected positive in three drunk driving cases, and the concentration were 195.49, 83.67 and 876.12 ng/mL, respectively., Conclusions: The established method has high sensitivity and specificity and the analysis results are accurate. It is suitable for the qualitative and quantitative analysis of PEth in whole blood.

The clinical randomized controlled trials(RCTs) of Chinese patent medicine in the treatment of chronic obstructive pulmonary disease(COPD) were reviewed and analyzed to provide references for clinical research, guideline development, policy formulation, and quality improvement of clinical evidence. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, SinoMed, Cochrane Library, PubMed, EMbase were searched for RCTs of Chinese patent medicine for COPD as a source of clinical evidence from database inception to December 31, 2019. The publication time, sample size, intervention and control measures, course of treatment, outcome indicators, and methodological quality of the trials were analyzed and evaluated. A total of 733 RCTs of Chinese patent medicine for COPD were included, among which 228 RCTs had a sample size higher than 100, accounting for 31.1% of total RCTs. Eighty-eight Chinese patent medicines were involved, including 40 oral medicines and 48 injections. A total of 327 RCTs mentioned intervention and control measures(Chinese patent medicine + conventional treatment vs conventional treatment), accounting for 43.0%. In addition, 94.40% of the RCTs reported the course of treatment, and 53.20% of the RCTs determined 8-14 d as the intervention course. The evaluation indicators adopted were numerous, among which physicochemical indicators(70.57%) and symptoms/signs(24.35%) were the most frequently employed. The operation of allocation concealment and blinding was not standard. Registration and the procedure related to ethics were mostly missing. The results indicate that there are prominent methodological problems in the clinical trials of Chinese patent medicine in the treatment of COPD, affecting the reliability and practicability of the trials. It is necessary to further standardize the design, implementation, and quality control of clinical trials of Chinese patent medicine in the treatment of COPD, highlight the clinical value of Chinese patent medicine for COPD, and improve the quality of evidence.

The present study reviewed the clinical randomized controlled trials(RCTs) of Chinese patent medicine for pneumonia to provide references for clinical research, guideline development, and policy formulation, and promote the quality improvement of clinical evidence. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, SinoMed were searched for RCTs of Chinese patent medicine for pneumonia from database inception to December 31, 2019. A total of 1 245 RCTs were included, involving 84 Chinese patent medicines, including 45 oral medicines and 39 injections. Specifically, 85.9% of RCTs had treatment course not exceeding 14 d; 43.3% of RCTs had a sample size of more than 100 cases and 6.1% of RCTs more than 200 cases; 13 types of interventions/controls were included in the RCTs, with Chinese patent medicine + western medicine vs western medicine as the top one used(32.6%). In outcome indicators, symptoms/signs(3 285) and physicochemical detection(2 066) were the most frequently applied. In the methodological evaluation, &quot;allocation concealment&quot; was not clearly described or mentioned in 71.2% of RCTs, and &quot;blinding&quot; in 23.9% of RCTs met the normative standards. Registration and research ethics were not clearly reported. There are many methodological deficiencies in terms of design and implementation in included RCTs, which may impact the reliability and practicability of the results of RCTs. Additionally, key standards were unclear(such as disease classification methods and selection of core outcome indicators). In conclusion, RCTs should give priority to the preciseness and scientificity of the protocol, strengthening quality control of the processes and accelerating the standardized research of key links.

The present study systematically collected, analyzed, and evaluated randomized controlled trial(RCT) of Chinese patent medicine in the treatment of heart failure to provide references for follow-up clinical research design, guideline update, and policy formulation, and promote the improvement of clinical evidence quality. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, VIP, Wanfang, SinoMed, PubMed, and Web of Science were searched for RCTs of Chinese patent medicine in the treatment of heart failure from database inception to December 31, 2020. The di-sease type, publication time, sample size, intervention/control setting, course of treatment, evaluation indexes, and methodological quality were analyzed and evaluated. A total of 1 631 RCTs were included, including 1 622 in Chinese and 9 in English. It was first published in 1995, with the largest number of publications in 2016. There were only 56 RCTs(3.43%) with a sample size≥200. Seventy-eight types of Chinese patent medicines were involved, including 49 types of oral drugs and 29 types of injections. There were 34 intervention/control protocols, which were dominated by Chinese patent medicine+conventional treatment vs conventional treatment, accounting for 28.51%(n=465). About 94.0% of RCTs reported the course of treatment, mainly 14-56 days. The evaluation indexes were mainly physical and chemical tests and symptoms/signs, and left ventricular ejection fraction(LVEF) was the most frequently used measurement index. In enumeration indexes, clinical efficacy(response rate) was used the most frequently. Methodologically, 92.0% of the research subjects were rated as high risk of blindness. There were only 13 RCTs(0.80%) reporting registered information. It is necessary to further standardize the design, implementation, and quality control of clinical studies in order to improve the quality of evidence and avoid research waste.

The clinical randomized controlled trial(RCT) of Chinese patent medicine in the treatment of influenza were reviewed and analyzed to provide basic information for clinical decision and related research. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, and Cochrane Library were searched for RCTs of Chinese patent medicine for influenza published from database inception to July 25, 2021. The publication time, sample size, intervention and control measures, course of treatment, outcome indicators, and methodological quality of the trials were analyzed and evaluated. Ninety-two RCTs of Chinese patent medicine for influenza published between 2005 and 2021, were included, among which 17 RCTs(18.48%) had a sample size higher than 200 and the average sample size was about 145. Twenty-seven Chinese patent medicines were involved, including twenty-one oral medicines and six injections. The Chinese patent medicines in trials reported in more than five papers included Lianhua Qingwen Capsules/Gra-nules, Tanreqing Injection, and Reduning Injection. Fourteen intervention protocols were reported, of which Chinese patent medicine+western medicine+conventional treatment vs western medicine+conventional treatment(20.65%) was the most frequently employed. Additionally, 85.87% of the RCTs reported the course of treatment, and 80.43% of the RCTs determined 3-7 d as the intervention course. Forty-five outcome indicators were extracted, which were used 434 times, including symptoms/signs, physicochemical detection, safety events, TCM symptoms/syndromes, quality of life, long-term prognosis, and economic evaluation. Symptoms/signs(61.52%) exhibited the highest frequency. Methodological problems were prevalent in the included trials. The findings reveal that there are few clinical trials on influenza treatment by Chinese patent medicine, and the methodological problems are prominent, affec-ting the reliability and practicability of the trials. In the future research, the value characteristics of Chinese patent medicine should be highlighted and the quality control in the whole process should be strengthened based on the scientific and rigorous design.

Increasing damage of pests in agriculture and forestry can arise both as a consequence of changes in local species and through the introduction of alien species. In this study, we used population genetics approaches to examine population processes of two pests of the tree-of-heaven trunk weevil (TTW), Eucryptorrhynchus brandti (Harold) and the tree-of-heaven root weevil (TRW), E .  scrobiculatus (Motschulsky) on the tree-of-heaven across their native range of China. We analyzed the population genetics of the two weevils based on ten highly polymorphic microsatellite markers. Population genetic diversity analysis showed strong population differentiation among populations of each species, with F ST ranges from 0.0197 to 0.6650 and from -0.0724 to 0.6845, respectively. Populations from the same geographic areas can be divided into different genetic clusters, and the same genetic cluster contained populations from different geographic populations, pointing to dispersal of the weevils possibly being human-mediated. Redundancy analysis showed that the independent effects of environment and geography could account for 93.94% and 29.70% of the explained genetic variance in TTW, and 41.90% and 55.73% of the explained genetic variance in TRW, respectively, indicating possible impacts of local climates on population genetic differentiation. Our study helps to uncover population genetic processes of these local pest species with relevance to control methods., Competing Interests: There are no conflicts of interest., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Organosilicone molecules represent important components of surfactants added to pesticides to improve pest control efficiency, but these molecules also have pesticidal properties in their own right. Here, we examined toxicity and control efficacy of Silwet 408, a trisiloxane ethoxylate-based surfactant, to the two-spotted spider mite (TSSM), Tetranychus urticae and its crop hosts. Silwet 408 was toxic to nymphs and adults of TSSM but did not affect eggs. Field trials showed that the control efficacy of 1000 mg/L Silwet 408 aqueous solution reached 96% one day after spraying but declined to 54% 14 days after spraying, comparable to 100 mg/L cyetpyrafen, a novel acaricide. A second spraying of 1000 mg/L Silwet 408 maintained control efficacy at 97% when measured 14 days after spraying. However, Silwet 408 was phytotoxic to eggplant, kidney bean, cucumber, and strawberry plants, although phytotoxicity to strawberry plants was relatively low and declined further seven days after application. Our study showed that while the organosilicone surfactant Silwet 408 could be used to control the TSSM, its phytotoxicity to crops should be considered.

The western flower thrips Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae) is an important invasive pest worldwide. Field-evolved resistance to the pesticide spinetoram is an increasing problem in the chemical control of this pest. Here, we examined changes in the frequency of a genetic mutation associated with spinetoram resistance, the G275E mutation in the acetylcholine receptor Foα6 , in 62 field populations collected from 2009 to 2021 across areas of China invaded by this pest. We found a low frequency of the G275E mutation in populations collected at the early invasion stage, in contrast to a high frequency in native USA populations. However, the frequency of the G275E mutation has increased to a high level in recently collected populations, with the mutation becoming fixed in some populations. There was a correlation between the frequency of the G275E mutation and resistance to spinetoram as characterized by median lethal concentration, although two populations were outliers. These results showed that G275E mutation is one of the mechanisms conferring spinetoram resistance in many invading populations in China. Ongoing dispersal of the WFT may have facilitated a rapid increase in the G275E mutation across China. Our study highlights the rapid evolution of pesticide resistance in an invasive species and points to a useful marker for molecular diagnostics of spinetoram resistance.

The Quaternary climatic oscillations are expected to have had strong impacts on the evolution of species. Although legacies of the Quaternary climates on population processes have been widely identified in diverse groups of species, adaptive genetic changes shaped during the Quaternary have been harder to decipher. Here, we assembled a chromosome-level genome of the oriental fruit moth and compared genomic variation among refugial and colonized populations of this species that diverged in the Pleistocene. High genomic diversity was maintained in refugial populations. Demographic analysis showed that the effective population size of refugial populations declined during the penultimate glacial maximum (PGM) but remained stable during the last glacial maximum (LGM), indicating a strong impact of the PGM rather than the LGM on this pest species. Genome scans identified one chromosomal inversion and a mutation of the circadian gene Clk on the neo-Z chromosome potentially related to the endemicity of a refugial population. In the colonized populations, genes in pathways of energy metabolism and wing development showed signatures of selection. These different genomic signatures of refugial and colonized populations point to multiple impacts of Quaternary climates on adaptation in an extant species., (© 2022. The Author(s).)

Oncofetal chondroitin sulfate expression plays an important role in the development of tumors and the pathogenesis of malaria in pregnancy. However, the biosynthesis and functions of these chondroitin sulfates, particularly the tissue-specific regulation either in tumors or placenta, have not been fully elucidated. Here, by examining the glycogenes availability in chondroitin sulfate biosynthesis such as xylosytransferase, chondroitin synthase, sulfotransferase, and epimerase, the conserved or differential CS glycosylation in normal, colorectal cancer (CRC), and placenta tissue were predicted. We found that the expression of seven chondroitin sulfate biosynthetic enzymes, namely B4GALT7, B3GALT6, B3GAT3, CHSY3, CHSY1, CHPF, and CHPF2, were significantly increased, while four other enzymes (XYLT1, CHST7, CHST15, and UST) were decreased in the colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) patients. In the human placenta, where the distinct chondroitin sulfate is specifically bound with VAR2CSA on Plasmodium parasite-infected RBC, eight chondroitin sulfate biosynthesis enzymes (CSGALNACT1, CSGALNACT2, CHSY3, CHSY1, CHPF, DSE, CHST11, and CHST3) were significantly higher than the normal colon tissue. The similarly up-regulated chondroitin synthases (CHSY1, CHSY3, and CHPF) in both cancer tissue and human placenta indicate an important role of the proteoglycan CS chains length for Plasmodium falciparum VAR2CSA protein binding. Interestingly, twelve highly expressed chondroitin sulfate enzymes were significantly correlated to worse outcomes (prognosis) in both COAD and READ. Furthermore, we showed that the levels of chondroitin sulfate enzymes are significantly correlated with the expression of immuno-regulators and immune infiltration levels in CRCs and placenta, and involved in multiple essential pathways, such as extracellular matrix organization, epithelial-mesenchymal transition, and cell adhesion. Our study provides novel insights into the oncofetal chondroitin sulfate biosynthesis regulation and identifies promising targets and biomarkers of immunotherapy for CRC and malaria in pregnancy., 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 Wu, He, Wang, Yang, Li, Deng, Cao, Zhang, Xue and Jia.)

Background: Nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV) associated cancer, exhibits an extremely high incidence in southern Chinese. Given that human leukocyte antigen (HLA) plays critical roles in antigen presentation and relates to NPC susceptibility, it is speculated that certain HLA variants may affect EBV reactivation, which is a key pathogenic factor of NPC. Therefore, we attempted to identify HLA alleles associated with the indicator of EBV reactivation, Zta-IgA, in healthy males from NPC endemic area., Methods: HLA alleles of 1078 healthy males in southern China from the 21-RCCP study were imputed using genome-wide single nucleotide polymorphism data. EBV Zta-IgA in blood samples were measured using an enzyme-linked immunosorbent assay. Multiple logistic regression analysis was used to evaluate the effect of HLA allele on Zta-IgA serological status and its potential joint association with smoking. The binding affinity for Zta-peptide was predicted using NetMHCIIpan 4.0., Results: HLA-DRB1*09:01 was found to be associated with a higher risk of Zta-IgA seropositivity (odds ratio = 1.80, 95% confidence interval = 1.32-2.45; p = 1.82 × 10 -4 ). Compared with non-smokers without HLA-DRB1*09:01, the effect size increased to 2.19- and 3.70-fold for the light and heavy smokers carrying HLA-DRB1*09:01, respectively. Furthermore, HLA-DRB1*09:01 showed a stronger binding affinity to Zta peptide than other HLA-DRB1 alleles., Conclusions: Our study highlighted the pivotal role of genetic HLA variants in EBV reactivation and the etiology of NPC. Smokers with HLA-DRB1*09:01 have a significantly higher risk of being Zta-IgA seropositive, which indicates the necessity of smoking cessation in certain high-risk populations and also provide clues for further research on the etiology of NPC., (© 2021 The Authors. The Journal of Gene Medicine published by John Wiley & Sons Ltd.)