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Abstract Objective This study aims to examine the impact of PE/PPE gene mutations on the transmission of Mycobacterium tuberculosis (M. tuberculosis) in China. Methods We collected the whole genome sequencing (WGS) data of 3202 M. tuberculosis isolates in China from 2007 to 2018 and investigated the clustering of strains from different lineages. To evaluate the potential role of PE/PPE gene mutations in the dissemination of the pathogen, we employed homoplastic analysis to detect homoplastic single nucleotide polymorphisms (SNPs) within these gene regions. Subsequently, logistic regression analysis was conducted to analyze the statistical association. Results Based on nationwide M. tuberculosis WGS data, it has been observed that the majority of the M. tuberculosis burden in China is caused by lineage 2 strains, followed by lineage 4. Lineage 2 exhibited a higher number of transmission clusters, totaling 446 clusters, of which 77 were cross-regional clusters. Conversely, there were only 52 transmission clusters in lineage 4, of which 9 were cross-regional clusters. In the analysis of lineage 2 isolates, regression results showed that 4 specific gene mutations, PE4 (position 190,394; c.46G > A), PE_PGRS10 (839,194; c.744 A > G), PE16 (1,607,005; c.620T > G) and PE_PGRS44 (2,921,883; c.333 C > A), were significantly associated with the transmission of M. tuberculosis. Mutations of PE_PGRS10 (839,334; c.884 A > G), PE_PGRS11 (847,613; c.1455G > C), PE_PGRS47 (3,054,724; c.811 A > G) and PPE66 (4,189,930; c.303G > C) exhibited significant associations with the cross-regional clusters. A total of 13 mutation positions showed a positive correlation with clustering size, indicating a positive association. For lineage 4 strains, no mutations were found to enhance transmission, but 2 mutation sites were identified as risk factors for cross-regional clusters. These included PE_PGRS4 (338,100; c.974 A > G) and PPE13 (976,897; c.1307 A > C). Conclusion Our results indicate that some PE/PPE gene mutations can increase the risk of M. tuberculosis transmission, which might provide a basis for controlling the spread of tuberculosis.

Objectives: This study aimed to describe the lineage-specific transmissibility and epidemiological migration of Mycobacterium tuberculosis in China. Methods: We curated a large set of whole-genome sequences from 3204 M. tuberculosis isolates, including thousands of newly sequenced genomes, and applied a series of metrics to compare the transmissibility of M. tuberculosis strains between lineages and sublineages. The countrywide transmission patterns of major lineages were explored. Results: We found that lineage 2 (L2) was the most prevalent lineage in China (85.7%), with the major sublineage 2.2.1 (80.9%), followed by lineage 4 (L4) (13.8%), which comprises major sublineages 4.2 (1.5%), 4.4 (6.2%) and 4.5 (5.8%). We showed evidence for frequent cross-regional spread and large cluster formation of L2.2.1 strains, whereas L4 strains were relatively geographically restricted in China. Next, we applied a series of genomic indices to evaluate M. tuberculosis strain transmissibility and uncovered higher transmissibility of L2.2.1 compared with the L2.2.2 and L4 sublineages. Phylogeographic analysis showed that southern, eastern, and northern China were highly connected regions for countrywide L2.2.1 strain spread. Conclusions: The present study provides insights into the different transmission and migration patterns of the major M. tuberculosis lineages in China and highlights that transmissible L2.2.1 is a threat to tuberculosis control.

ABSTRACTObjectives We investigated the genetic diversities and lineage-specific transmission dynamics of multidrug-resistant tuberculosis (MDR-TB), with the goal of determining the potential factors driving the MDR epidemics in China.Methods We curated a large nationwide Mycobacterium tuberculosis (M. tuberculosis) whole genome sequence data set, including 1313 MDR strains. We reconstructed the phylogeny and mapped the transmission networks of MDR-TB across China using Bayesian inference. To identify drug-resistance variants linked to enhanced transmissibility, we employed ordinary least-squares (OLS) regression analysis.Result The majority of MDR-TB strains in China belong to lineage 2.2.1. Transmission chain analysis has indicated that the repeated and frequent transmission of L2.2.1 plays a central role in the establishment of MDR epidemic in China, but no occurrence of a large predominant MDR outbreak was detected. Using OLS regression, the most common single nucleotide polymorphisms (SNPs) associated with resistance to isoniazid (katG_p.Ser315Thr and katG_p.Ser315Asn) and rifampicin (rpoB_p.Ser450Leu, rpoB_p.His445Tyr, rpoB_p.His445Arg, rpoB_p.His445Asp, and rpoB_p.His445Asn) were more likely to be found in L2 clustered strains. Several putative compensatory mutations in rpoA, rpoC, and katG were significantly associated with clustering. The eastern, central, and southern regions of China had a high level of connectivity for the migration of L2 MDR strains throughout the country. The skyline plot showed distinct population size expansion dynamics for MDR-TB lineages in China.Conclusion MDR-TB epidemic in China is predominantly driven by the spread of highly transmissible Beijing strains. A range of drug-resistance mutations of L2 MDR-TB strains displayed minimal fitness costs and may facilitate their transmission.

Introduction: Tuberculosis (TB) is an infectious disease caused by a bacterium called Mycobacterium tuberculosis (Mtb). Previous studies have primarily focused on the transmissibility of multidrug-resistant (MDR) or extensively drug-resistant (XDR) Mtb. However, variations in virulence across Mtb lineages may also account for differences in transmissibility. In Mtb, polyketide synthase (PKS) genes encode large multifunctional proteins which have been shown to be major mycobacterial virulence factors. Therefore, this study aimed to identify the role of PKS mutations in TB transmission and assess its risk and characteristics.Methods: Whole genome sequences (WGSs) data from 3,204 Mtb isolates was collected from 2011 to 2019 in China. Whole genome single nucleotide polymorphism (SNP) profiles were used for phylogenetic tree analysis. Putative transmission clusters (≤10 SNPs) were identified. To identify the role of PKS mutations in TB transmission, we compared SNPs in the PKS gene region between “clustered isolates” and “non-clustered isolates” in different lineages.Results: Cluster-associated mutations in ppsA, pks12, and pks13 were identified among different lineage isolates. They were statistically significant among clustered strains, indicating that they may enhance the transmissibility of Mtb.Conclusion: Overall, this study provides new insights into the function of PKS and its localization in M. tuberculosis. The study found that ppsA, pks12, and pks13 may contribute to disease progression and higher transmission of certain strains. We also discussed the prospective use of mutant ppsA, pks12, and pks13 genes as drug targets.

Long non-coding RNA (LncRNA) THOR (Lnc-THOR) is expressed in testis and multiple human malignancies. Lnc-THOR association with IGF2BP1 (IGF2 mRNA-binding protein 1) is essential for stabilization and transcription of IGF2BP1 targeted mRNAs. We tested its expression and potential functions in non-small cell lung cancer (NSCLC). In primary NSCLC cells and established cell lines, Lnc-THOR shRNA or CRISPR/Cas9-mediated knockout (KO) downregulated IGF2BP1 target mRNAs (IGF2, Gli1, Myc and SOX9), inhibiting cell viability, growth, proliferation, migration and invasion. Significant apoptosis activation was detected in Lnc-THOR-silenced/-KO NSCLC cells. Conversely, ectopic overexpression of Lnc-THOR upregulated IGF2BP1 mRNA targets and enhanced NSCLC cell proliferation, migration and invasion. RNA-immunoprecipitation and RNA pull-down assay results confirmed the direct binding between Lnc-THOR and IGF2BP1 protein in NSCLC cells. Lnc-THOR silencing and overexpression were ineffective in IGF2BP1-KO NSCLC cells. Forced IGF2BP1 overexpression failed to rescue Lnc-THOR-KO NSCLC cells. In vivo, intratumoral injection of Lnc-THOR shRNA adeno-associated virus potently inhibited A549 xenograft tumor growth in nude mice. At last we show that Lnc-THOR is overexpressed in multiple NSCLC tissues and established/primary NSCLC cells. Collectively, these results highlighted the ability of Lnc-THOR in promoting NSCLC cell growth by associating with IGF2BP1, suggesting that Lnc-THOR represents a promising therapeutic target of NSCLC.

Modern pollen records have been used to successfully distinguish between specific prairie types in North America. Whether the pollen records can be used to detect the occurrence of Eurasian steppe, or even to further delimit various steppe types was until now unclear. Here we characterized modern pollen assemblages of meadow steppe, typical steppe and desert steppe from eastern Eurasia along an ecological humidity gradient. The multivariate ordination of the pollen data indicated that Eurasian steppe types could be clearly differentiated. The different steppe types could be distinguished primarily by xerophilous elements in the pollen assemblages. Redundancy analysis indicated that the relative abundances of Ephedra, Tamarix, Nitraria and Zygophyllaceae were positively correlated with aridity. The relative abundances of Ephedra increased from meadow steppe to typical steppe and desert steppe. Tamarix and Zygophyllaceae were found in both typical steppe and desert steppe, but not in meadow steppe. Nitraria was only found in desert steppe. The relative abundances of xerophilous elements were greater in desert steppe than in typical steppe. These findings indicate that Eurasian steppe types can be differentiated based on recent pollen rain.

IntroductionPanax notoginseng, a medicinal herb in China, is attacked by several pathogens during its cultivation. Dazomet (DZ) is a soil fumigant that is effective in controlling soil-borne pathogens, but its long-term effects on P. notoginseng growth and soil properties are unknown.MethodsWe conducted field experiments over two consecutive years to assess the impact of three concentrations of DZ fumigation (35 kg/666.7 m2, 40 kg/666.7 m2, and 45 kg/666.7 m2) on soil physicochemical properties, microbial diversity, and P. notoginseng growth. Correlation analyses were performed between microbial community changes and soil properties, and functional predictions for soil microorganisms were conducted.ResultsDZ fumigation increased total nitrogen, total phosphorus, total potassium, available phosphorus, available potassium, and ammonia nitrogen levels in the soil. DZ fumigation promoted the nutrient accumulation and improvement of agronomic traits of P. notoginseng, resulted in a 2.83–3.81X yield increase, with the highest total saponin content increasing by 24.06%. And the 40 kg/666.7 m2 treatment had the most favorable impact on P. notoginseng growth and saponin accumulation. After DZ fumigation, there was a decrease in the relative abundance of pathogenic fungi such as Fusarium, Plectosphaerella, and Ilyonectria, while beneficial bacteria such as Ramlibacter, Burkholderia, and Rhodanobacteria increased. The effects of fumigation on soil microorganisms and soil physicochemical properties persisted for 18 months post-fumigation. DZ fumigation enhanced the relative abundance of bacteria involved in the biosynthesis of secondary metabolites and arbuscular mycorrhizal fungi, reduced the relative abundance of plant–animal pathogenic fungi, reduced the occurrence of soil-borne diseases.ConclusionIn conclusion, DZ fumigation enhanced soil physicochemical properties, increased the proportion of beneficial bacteria in the soil, and rebalanced soil microorganism populations, consequently improving the growth environment of P. notoginseng and enhancing its growth, yield, and quality. This study offers a theoretical foundation for DZ fumigation as a potential solution to the continuous cropping issue in perennial medicinal plants such as P. notoginseng.

Introduction Preliminary evidence from clinical observations suggests that Tai Chi exercise may offer potential benefits for patients with chronic coronary syndrom (CCS). However, the advantages for CCS patients to practice Tai Chi exercise as rehabilitation have not been rigorously tested and there is a lack of consensus on its benefits. This study aims to develop an innovative Tai Chi Cardiac Rehabilitation Program (TCCRP) for CCS patients and to assess the efficacy, safety and acceptability of the programme. Methods and analysis We propose to conduct a multicentre randomised controlled clinical trial comprising of 150 participants with CCS. The patients will be randomly assigned in a 1:1 ratio into two groups. The intervention group will participate in a supervised TCCRP held three times a week for 3 months. The control group will receive supervised conventional exercise rehabilitation held three times a week for 3 months. The primary and secondary outcomes will be assessed at baseline, 1 month, 3 months after intervention and after an additional 3-month follow-up period. Primary outcome measures will include a score of 36-Item Short Form Survey and Chinese Perceived Stress Scale. The secondary outcome measures will include body composition, cardiopulmonary exercise test, respiratory muscle function, locomotor skills, echocardiogram, New York Heart Association classification, heart rate recovery time and laboratory examination. Other measures also include Seattle Angina Scale, Pittsburgh Sleep Quality Index, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 and Berg Balance Scale. All adverse events will be recorded and analysed. Ethics and dissemination This study conforms to the principles of the Declaration of Helsinki and relevant ethical guidelines. Ethical approval has been obtained from the Ethics Committee of Chinese People’s Libration Army General Hospital (approval number: S2019-060-02). Findings from this study will be published and presented at conferences for widespread dissemination of the results. [ABSTRACT FROM AUTHOR]

Glaucoma is a common irreversible blinding eye disease, pathological elevated intraocular pressure is the main clinical feature. The formation of intraocular pressure, related to aqueous circulation, will be pathologically elevated when the aqueous cycle is abnormal. Trabecular network, which plays a key role in maintaining normal intraocular pressure, is the main component of aqueous outflow channel. Imbalance of oxidative stress manifested as oxidation and antioxidant effects is a direct risk factor for elevated intraocular pressure in glaucoma. When it comes to the trabecular meshwork cells, a series of changes such as deposition and degeneration of extracellular matrix, autophagy and aging will eventually occur, and finally the dysfunction of trabecular meshwork cells and increased aqueous outflow resistance, causing intraocular pressure pathological elevated. In this paper, we reviewed the research progress on the relationship between oxidative stress in trabecular meshwork cells and the pathogenesis of glaucoma, in order to provide evidence for further research and reference for exploring the pathogenesis, prevention and treatment of glaucoma.

AIM: To investigate the association of axial length (AL), lens thickness (LT), and lens vault (LV) with postoperative anterior chamber angle metrics after laser peripheral iridotomy (LPI). METHODS: Prospective observational study of 69 patients (97 eyes) were diagnosed as primary angle-closure suspect (PACS), primary angle closure (PAC) or primary angle-closure glaucoma (PACG). AL, LT, anterior central chamber depth (ACD), angle opening distance (AOD), trabecular iris angle (TIA), and angle recess area (ARA) were measured before and 1wk after LPI. The association between AL, LT, LV with ACD, AOD, TIA, ARA were analyzed by comparing the differences between preoperative and postoperative measurements for anterior segment biometric parameters. RESULTS: ACD, AOD, TIA, and ARA were significantly increased after LPI (all P

Introduction Preliminary evidence from clinical observations suggests that Tai Chi exercise may offer potential benefits for patients with chronic coronary syndrom (CCS). However, the advantages for CCS patients to practice Tai Chi exercise as rehabilitation have not been rigorously tested and there is a lack of consensus on its benefits. This study aims to develop an innovative Tai Chi Cardiac Rehabilitation Program (TCCRP) for CCS patients and to assess the efficacy, safety and acceptability of the programme.Methods and analysis We propose to conduct a multicentre randomised controlled clinical trial comprising of 150 participants with CCS. The patients will be randomly assigned in a 1:1 ratio into two groups. The intervention group will participate in a supervised TCCRP held three times a week for 3 months. The control group will receive supervised conventional exercise rehabilitation held three times a week for 3 months. The primary and secondary outcomes will be assessed at baseline, 1 month, 3 months after intervention and after an additional 3-month follow-up period. Primary outcome measures will include a score of 36-Item Short Form Survey and Chinese Perceived Stress Scale. The secondary outcome measures will include body composition, cardiopulmonary exercise test, respiratory muscle function, locomotor skills, echocardiogram, New York Heart Association classification, heart rate recovery time and laboratory examination. Other measures also include Seattle Angina Scale, Pittsburgh Sleep Quality Index, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 and Berg Balance Scale. All adverse events will be recorded and analysed.Ethics and dissemination This study conforms to the principles of the Declaration of Helsinki and relevant ethical guidelines. Ethical approval has been obtained from the Ethics Committee of Chinese People’s Libration Army General Hospital (approval number: S2019-060-02). Findings from this study will be published and presented at conferences for widespread dissemination of the results.Trial registration number NCT03936504.