Mosquitoes are of great medical significance as vectors of many deadly diseases. Mitogenomes have been widely used in phylogenetic studies, but mitogenome knowledge within the family Culicidae is limited, and Culicidae phylogeny is far from resolved. In this study, we surveyed the mitogenomes of 149 Culicidae species, including 7 newly sequenced species. Comparative analysis of 149 mosquito mitogenomes shows gene composition and order to be identical to that of an ancestral insect, and the AT bias, length variation, and codon usage are all consistent with that of other reported Dipteran mitogenomes. Phylogenetic analyses based on the DNA sequences of the 13 protein-coding genes from the 149 species robustly support the monophyly of the subfamily Anophelinae and the tribes Aedini, Culicini, Mansoniini, Sabethini, and Toxorhynchitini. To resolve ambiguous relationships between clades within the subfamily Culicinae, we performed topological tests and show that Aedini is a sister to Culicini and that Uranotaeniini is a sister to (Mansoniini + (Toxorhynchitini + Sabethini)). In addition, we estimated divergence times using a Bayesian relaxation clock based on the sequence data and 3 fossil calibration points. The results show mosquitoes diverged during the Early Jurassic with massive Culicinae radiations during the Cretaceous, coincident with the emergence of angiosperms and the burst of mammals and birds. Overall, this study, which uses the largest number of Culicidae mitogenomes sequenced to date, comprehensively reveals the mitogenome characteristics and mitogenome-based phylogeny and divergence times of Culicidae, providing information for further studies on the mitogenome, phylogeny, evolution, and taxonomic revision of Culicidae.
Culicidae , Genome, Mitochondrial , Animals , Culicidae/genetics , Phylogeny , Bayes Theorem , Mosquito Vectors/genetics , Mammals/genetics
A cross-sectional study method combined with two types of traditional Chinese medicine(TCM) syndrome differentiation methods was adopted to investigate the clinical symptoms and distribution characteristics of TCM syndromes in patients with pulmonary nodules from the perspectives of number, size, nature, and stability of pulmonary nodules by using the χ~2 test, systematic clustering and Apriori algorithm correlation analysis. The common clinical symptoms of pulmonary nodules were fatigue(77.35%) and irritability(75.40%), and 40 symptoms were clustered into 3 groups(digestive system symptoms, respiratory system symptoms, and emotional and systemic symptoms) and 8 major symptom categories. The proportion of cold and heat in complexity syndrome(63.43%) was higher based on cold-heat syndrome differentiation. The top two syndromes were Qi deficiency syndrome(88.03%) and Qi depression syndrome(83.17%) based on disease syndrome differentiation. Yang deficiency syndrome(60.52%) was more than Yin deficiency syndrome(50.16%). There were higher proportions of phlegm syndrome(78.67%) and Yang deficiency syndrome(69.33%) of so-litary pulmonary nodules in terms of the number of pulmonary nodules. In terms of size, the proportion of phlegm syndrome decreased as the mean diameter of pulmonary nodules increased, while the proportions of Yang deficiency syndrome and blood stasis syndrome increased. The distribution of Qi depression syndrome was more in those with mean diameter<10 mm(85.02%, P=0.044) and cold syndrome was more in those with mean diameter ≥10 mm(16.67%, P=0.024). In terms of the nature of pulmonary nodules, the proportions of Qi depression syndrome and heat syndrome decreased with the increase in solid components of pulmonary nodules, while the proportions of Yin deficiency syndrome and cold and heat in complexity syndrome increased. The blood stasis syndrome accounted for a higher proportion of pulmonary nodules with solid components. In terms of the stability of pulmonary nodules, dampness syndrome(72.97%), blood stasis syndrome(37.84%), and cold and heat in complexity syndrome(70.27%) accounted for higher proportions. In addition, patients with new nodules presented higher proportions in Qi inversion syndrome(52.00%, P=0.007) and cold and heat in complexity syndrome(66.00%, P=0.008). Meanwhile, 11 syndromes were associated and 4 common compound syndromes were obtained(Qi deficiency and depression syndrome, Qi depression and phlegm coagulation syndrome, Qi deficiency and phlegm coagulation syndrome, and Qi deficiency and dampness obstruction syndrome). Qi deficiency syndrome and Qi depression syndrome could be associated with other syndromes. The results show that the main clinical symptoms of pulmonary nodules are fatigue and irritability. The main TCM syndromes of pulmonary nodules are Qi deficiency syndrome, Qi depression syndrome, Yang deficiency syndrome, and cold and heat in complexity syndrome. The distribution of TCM syndromes is significantly correlated with the size of pulmonary nodules and the presence or absence of new nodules. The common compound syndromes are Qi deficiency and depression syndrome, Qi depression and phlegm coagulation syndrome, Qi deficiency and phlegm coagulation syndrome, and Qi deficiency and dampness obstruction syndrome.
Medicine, Chinese Traditional , Yin Deficiency , Humans , Yin Deficiency/diagnosis , Yang Deficiency/diagnosis , Cross-Sectional Studies , Syndrome
Myeloid-derived suppressor cells (MDSCs), major components maintaining the immune suppressive microenvironment in lung cancer, are relevant to the invasion, metastasis, and poor prognosis of lung cancer, through the regulation of epithelial-mesenchymal transition, remodeling of the immune microenvironment, and regulation of angiogenesis. MDSCs regulate T-cell immune functions by maintaining a strong immunosuppressive microenvironment and promoting tumor invasion. This raises the question of whether reversing the immunosuppressive effect of MDSCs on T cells can improve lung cancer treatment. To understand this further, this review explores the interactions and specific mechanisms of different MDSCs subsets, including regulatory T cells, T helper cells, CD8 + T cells, natural killer T cells, and exhausted T cells, as part of the lung cancer immune microenvironment. Second, it focuses on the guiding significance confirmed via clinical liquid biopsy and tissue biopsy that different MDSC subsets improve the prognosis of lung cancer. Finally, we conclude that targeting MDSCs through action targets or signaling pathways can help regulate T-cell immune functions and suppress T-cell exhaustion. In addition, immune checkpoint inhibitors targeting MDSCs may serve as a new approach for enhancing the efficiency of immunotherapy and targeted therapy for lung cancer in the future, providing better comprehensive options for lung cancer treatment.
The subfamily Eumeninae is a large group of fierce predatory insects that prey mainly on the larvae of Lepidoptera pests. Because of the highly similar morphologies of the genus Rhynchium and its related genera in the subfamily, including Rhynchium Spinola, Allorhynchium van der Vecht, Anterhynchium de Saussure, Pararrhynchium de Saussure, it is essential to delineate their relationships. A previous phylogenetic analysis based on mitochondrial genomes suggested the inconsistent relationships of these genera under traditional classification based on morphological characters. In this study, we first used single-copy orthologs [USCO] and ultraconserved elements [UCE] extracted from 10 newly sequenced low-coverage whole genomes to resolve the phylogenetic relationships of the above genera. The newly sequenced genomes are 152.99 Mb to 211.49 Mb in size with high completeness (BUSCO complete: 91.5-95.6%) and G + C content (36.31-38.76%). Based on extracted 5811 USCOs and 2312 UCEs, the phylogenetic relationships of Rhynchium and its related genera were: ((Allorhynchium + Lissodynerus) + (Pararrhynchium + (Anterhynchium + (Dirhynchium + Rhynchium)))), which was consistent with the mitochondrial genome results. The results supported the genus Rhynchium as monophyletic, whereas Anterhynchium was recovered as paraphyletic, with Anterhynchium (Dirhynchium) as a sister to Rhynchium and hence deserving generic status; In addition, in the genus Pararrhynchium, P. septemfasciatus feanus and P. venkataramani were separated, not clustered on a branch, just as P. septemfasciatus feanus was not together with P. striatum based on mitochondrial genomes. Since Lissodynerus septemfasciatus, the type species of the genus Lissodynerus, was transferred to Pararrhynchium, it is considered that the genus Lissodynerus should be restituted as a valid genus, not a synonym of Pararrhynchium.
The Nymphalidae family of cosmopolitan butterflies (Lepidoptera) comprises approximately 7200 species found on all continents and in all habitats. However, debate persists regarding the phylogenetic relationships within this family. In this study, we assembled and annotated eight mitogenomes of Nymphalidae, constituting the first report of complete mitogenomes for this family. Comparative analysis of 105 mitochondrial genomes revealed that the gene compositions and orders were identical to the ancestral insect mitogenome, except for Callerebia polyphemus trnV being before trnL and Limenitis homeyeri having two trnL genes. The results regarding length variation, AT bias, and codon usage were consistent with previous reports on butterfly mitogenomes. Our analysis indicated that the subfamilies Limenitinae, Nymphalinae, Apaturinae, Satyrinae, Charaxinae, Heliconiinae, and Danainae are monophyletic, while the subfamily the subfamily Cyrestinae is polyphyletic. Danainae is the base of the phylogenetic tree. At the tribe level, Euthaliini in Limenitinae; Melitaeini and Kallimini in Nymphalinae; Pseudergolini in Cyrestinae; Mycalesini, Coenonymphini, Ypthimini, Satyrini, and Melanitini in Satyrinae; and Charaxini in Charaxinae are regarded as monophyletic groups. However, the tribe Lethini in Satyrinae is paraphyletic, while the tribes Limenitini and Neptini in Limenitinae, Nymphalini and Hypolimni in Nymphalinae, and Danaini and Euploeini in Danainae are polyphyletic. This study is the first to report the gene features and phylogenetic relationships of the Nymphalidae family based on mitogenome analysis, providing a foundation for future studies of population genetics and phylogenetic relationships within this family.
Butterflies , Genome, Mitochondrial , Animals , Butterflies/genetics , Phylogeny , Genome, Mitochondrial/genetics
Cockroaches, an ancient and diverse group of insects on earth that originated in the Carboniferous, displays a wide array of morphology or biology diversity. The spermatheca is an organ of the insect reproductive system; the diversity of spermathecae might be the adaption to different mating and sperm storage strategies. Yet a consensus about the phylogenetic relationships among the main lineages of Blattodea and the evolution of spermatheca has not been reached until now. Here we added the transcriptome data of Anaplectidae for the first time and supplemented other family level groups (such as Blaberidae, Corydiidae) to address the pending issues. Our results showed that Blattoidea was recovered as sister to Corydioidea, which was strongly supported by molecular evidence. In Blattoidea, (Lamproblattidae + Anaplectidae) + (Cryptocercidae + Termitoidae) was strongly supported by our molecular data. In Blaberoidea, Pseudophyllodromiidae and Blaberidae were recovered to be monophyletic, while Blattellidae was found to be paraphyletic with respect to Malaccina. Ectobius sylvestris + Malaccina discoidalis formed the sister group to other Blaberoidea; Blattellidae (except Malaccina discoidalis) + Nyctiboridae was found as the sister of Blaberidae. Corydiidae was recovered to be non-monophyletic due to the embedding of Nocticola sp. Our ASR analysis of spermatheca suggested that primary spermathecae were present in the common ancestor, and it transformed at least six times during the evolutionary history of Blattodea. The evolution of spermatheca could be described as a unidirectional trend: the increased size to accommodate more sperm. Furthermore, major splits within the existing genera of cockroaches occurred in the Upper Paleogene to Neogene. Our study provides strong support for the relationship among three superfamilies and offers some new insights into the phylogeny of cockroaches. Meanwhile, this study also provides basic knowledge on the evolution of spermathecae and reproductive patterns.
Cockroaches , Animals , Male , Phylogeny , Semen
OBJECTIVE: To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival (PFS) and overall survival (OS) of limited-stage small cell lung cancer (LS-SCLC) patients after the first-line chemoradiotherapy. METHODS: The data of 67 LS-SCLC patients who received combined treatment of CM and Western medicine (WM) between January 2013 and May 2020 at the outpatient clinic of Guang'anmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method (Kaplan-Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time. RESULTS: The median PFS in the CM and WM combination treatment group and the WM group were 19 months (95% CI: 12.357-25.643) vs. 9 months (95% CI: 5.957-12.043), HR=0.43 (95% CI: 0.27-0.69, P<0.001), respectively. The median OS in the CM and WM combination group and the WM group were 34 months (95% CI could not be calculated) vs. 18.63 months (95% CI: 16.425-20.835), HR=0.40 (95% CI: 0.24-0.66, P<0.001), respectively. Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months (P<0.001). CONCLUSION: The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone. (Registration No. ChiCTR2200056616).
Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Small Cell Lung Carcinoma/drug therapy , Lung Neoplasms/drug therapy , Retrospective Studies , Prognosis , Combined Modality Therapy
BACKGROUND: Glutathione S-transferases (GSTs), a multifunctional protein family, are involved in insecticide resistance. However, a systematic analysis of GSTs in Anopheles sinensis, an important vector for malaria transmission, is lacking. In this study, we investigated the diversity and characteristics of GST genes, and analyzed their expression patterns and functions associated with insecticide resistance in this species. RESULTS: We identified 32 putative cytosolic and three putative microsomal GST genes in the An. sinensis genome. Transcriptome analysis showed that GSTs were highly expressed in larvae, and mainly expressed in the antennae, midgut and Malpighian tubules of adults. In addition, we found that GSTd2 and GSTe2 were significantly upregulated in four An. sinensis pyrethroid-resistant field populations. Furthermore, silencing of GSTd2 and GSTe2 significantly increased the susceptibility of An. sinensis to deltamethrin, and recombinant GSTd2 and GSTe2 exhibited high enzymatic activity in the metabolism of 1-chloro-2,4-dinitrobenzene and dichlorodiphenyltrichloroethane (DDT). CONCLUSION: These results showed that GSTs are involved in the development of insecticide resistance in An. sinensis through transcriptional overexpression and enzymatic metabolization, facilitating our understanding of insecticide resistance in insects. © 2022 Society of Chemical Industry.
Anopheles , Insecticides , Malaria , Pyrethrins , Animals , DDT , Glutathione Transferase/genetics , Glutathione Transferase/metabolism , Insecticide Resistance/genetics , Insecticides/pharmacology , Mosquito Vectors/genetics , Pyrethrins/pharmacology
Objective. To investigate the treatment effect and treatment length of Chinese herbal decoction (CHD) as maintenance therapy on patients with extensive-stage small-cell lung cancer (ES-SCLC) and to reflect the real syndrome differentiation (Bian Zheng) practices of traditional Chinese medicine (TCM). Patients and Methods. Different CHDs were prescribed for each patient based on syndrome differentiation. The length of CHD treatment was divided into two phases for analyzing progression-free survival (PFS) and postprogression survival (PPS). Results. Three hundred and fifty-seven CHDs were prescribed based on syndrome differentiation during the study period. Median PFS was significantly longer in patients who received CHD >3 months than patients who received CHD ≤3 months in the first phase (8.7 months versus 4.5 months; hazard ratio (HR), 0.52; 95% confidence interval (CI), 0.41-0.99; P = 0.0009). Median PPS was significantly longer in patients who received CHD >7 months than patients who received CHD ≤7 months in the second phase (11.7 months versus 5.1 months; HR, 2.32; 95% CI, 1.90-2.74; P = 0.002). Conclusion. CHD could improve PFS and PPS, which are closely related to treatment time and deepness of response of first-line therapy. In addition, CHD could improve body function and keep patients in a relatively stable state.
