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Elucidating the cold tolerance mechanism of Paeonia lactiflora, which is one of the most valuable ornamental and medicinal plants in Asia, fundamentally impacts its breeding and production. The glycerol-3-phosphate acyltransferase (GPAT) gene plays a pivotal role in cold resistance in a variety of plant species. Here, we cloned the P. lactiflora GPAT gene, determined its expression pattern, and tested its role in cold resistance. We obtained the full-length P. lactiflora GPAT gene using tissue-cultured seedlings and real-time polymerase chain reaction and rapid amplification of cDNA ends analyses. We named this gene PlGPAT in P. lactiflora. Phylogenetic analysis indicates that the PlGPAT gene is closely related with the GPAT genes in core eudicots. The phylogenetic tree containing 31 angiosperm species based on GPAT protein sequences is largely consistent with the known phylogeny in flowering plants. We conducted a time-course PlGPAT expression analysis and demonstrated that PlGPAT expression is correlated with low-temperature stress. Our results suggest that the PlGPAT gene plays an important role in regulating cold resistance in P. lactiflora. [ABSTRACT FROM AUTHOR]

Cladribine tablets have been approved in many countries for the treatment of patients with various forms of relapsing multiple sclerosis (MS). Cladribine has a unique pharmacokinetic/pharmacodynamic (PK/PD) profile with a short elimination half‐life (~ 1 day) relative to a prolonged PD effect on specific immune cells (most notably a reversible reduction in B and T lymphocyte counts). This results in a short dosing schedule (up to 20 days over 2 years of treatment) to sustain efficacy for at least another 2 years. Global clinical studies were conducted primarily in White patients, in part due to the distinctly higher prevalence of MS in White patients. Given the very low prevalence in Asian countries, MS is considered as a rare disease there. In spite of the limited participation of Asian patients, to demonstrate favorable benefit/risk profile in the treatment of MS demanded application of a Totality of Evidence approach to assess ethnic sensitivity for informing regulatory filings in Asian countries and supporting clinical use of cladribine in Asian patients. Population PD modeling and simulation of treatment‐related reduction in absolute lymphocyte count, as a mechanism‐related biomarker of drug effect, confirmed consistent PDs in Asian and non‐Asian patients with MS, supporting absence of ethnic sensitivity and a common dosage across populations. Through this example, we demonstrate the value of holistic integration of all available data using a model‐informed drug development (MIDD) framework and a Totality of Evidence mindset to evaluate ethnic sensitivity in support of Asia‐inclusive development and use of the drug across populations. [ABSTRACT FROM AUTHOR]

[Display omitted] • More 3.0–2.9 Ga basement rocks were recognized in the Longgang Block, the Eastern Block of the North China Craton. • The protolith of quartzite of the Langzishan Formation was deposited at 2.47–2.2 Ga, older than its overlying pelites of 2.2–2.17 Ga. • The tectonic regime of the Eastern Block changed from a collisional setting to a passive continental margin, and then to an active continental margin at 2.47–2.17 Ga. As one of the most ancient cratons in Asia, the North China Craton (NCC) provides an opportunity to examine the evolution of the early earth. However, it is poorly known about the tectonic setting of the Eastern Block of the NCC at 2.47–2.17 Ga. In this study, zircon U-Pb dating was conducted to constrain the provenance, depositional age, and depositional environment of the Langzishan Formation in the Liaodong peninsula, to investigate the tectonic setting of the Eastern Block during the earliest Paleoproterozoic. Provenance analysis suggests that the basal sandstones (protolith of quartzite) in the Langzishan Formation were sourced from 3.8 to 2.5 Ga continental crust, while the overlying sandstone and pelite units were sourced exclusively from 2.5 Ga continental crust. The distribution of detrital zircon ages shows that the basal sandstones of the Langzishan Formation were deposited at 2.47–2.2 Ga, during which the tectonic setting changed from an early collisional setting (2.47–2.35 Ga) to a stable continental margin (2.35–2.2 Ga), whereas pelites in the upper layer of the Langzihsan Formation were deposited at 2.2–2.17 Ga, and also experienced a transition in tectonic setting from a passive continental margin to an active continental margin. The Langzishan Formation is believed to be the lowest sedimentary unit in the Eastern Block. The transition of tectonic setting of this formation shows that the Eastern Block probably has undergone the same transition at 2.47–2.17 Ga, from a collisional setting to a passive continental margin, and then to an active continental margin, possibly related to both onset of the 2.3–2.2 Ga Paleoproterozoic tectono-magmatic lull (TML) and its cessation. [ABSTRACT FROM AUTHOR]

Background. Platinum-based chemotherapy plays an antitumor role by damaging DNA. X-ray repair crosscomplementing protein 1 (XRCC1) participates in DNA repair and thus affects the sensitivity to platinum drugs. Two polymorphisms of XRCC1, rs25487 (Arg399Gln) and rs1799782 (Arg194Trp), have been widely studied for the association with clinical outcomes of platinum-based chemotherapy in Asian patients with non-small-cell lung cancer (NSCLC), but the results remain inconclusive. Thus, we performed the present meta-analysis. Methods. Literature search was performed in PubMed, Web of Science, and EMBASE up to June 2019. Odds ratios (ORs) for objective response ratio (ORR), Cox proportional hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS), and the corresponding 95% confidence intervals (95% CIs) were calculated to assess the association strengths between XRCC1 polymorphisms and clinical outcomes. Comparisons were performed in homozygous, heterozygous, dominant, and recessive models. Results. Finally, a total of 23 studies involving 5567 patients were included in the meta-analysis. Compared to ArgArg of rs25487, GlnGln (OR = 1.71 , 95% CI: 1.16-2.52, p =.007 , I 2 = 56.8 %) and GlnArg (OR = 1.23 , 95% CI: 1.07-1.40, p =.003 , I 2 = 29.0 %) were associated with higher ORR. Meanwhile, GlnGln indicated a favorable OS (HR = 0.60 , 95% CI: 0.40-0.88) and PFS (HR = 0.64 , 95% CI: 0.46-0.90). We also found positive associations between rs1799782 and ORR in all comparison models with low between-study heterogeneity. The association strength increased with the number of variant alleles (TrpTrp vs. ArgArg: OR = 1.73 , 95% CI:1.31-2.27; TrpArg vs. ArgArg: OR = 1.28 , 95% CI: 1.06-1.55), suggesting a gene dosage effect. In addition, TrpTrp predicted a longer OS. Conclusion. Our results showed that rs25487 and rs1799782 of XRCC1 are potential markers to predict clinical outcomes of platinum-based chemotherapy in Asian patients with NSCLC. [ABSTRACT FROM AUTHOR]

Background: China has a substantial tuberculosis (TB) disease burden and an aging population. Seniors have a higher risk of developing TB disease compared to younger age groups. Active case finding (ACF) could help identify seniors with TB disease. Methods: From March to June 2017, we included ACF during annual physical check-ups for persons aged ≥ 65 years in Bayi, Sichuan Province. Seniors with clinical TB symptoms (i.e., cough lasting ≥ 2 weeks and/or hemoptysis) or one or more risk factors (e.g., previous TB disease, diabetes, and heavy alcohol consumption) were offered chest x-rays. We used acid-Fast Bacilli smear and solid culture laboratory testing for TB confirmation. We calculated the yield (i.e., cases identified among seniors screened) and cost per new each TB case detected. Focus group-interviews were conducted with health care workers and seniors to evaluate project acceptability. Participation rates and acceptability were used to assess feasibility. Results: Of the 2,393 seniors residing in Bayi, 2,049 (85.6%) were enrolled in the pilot project. Of these seniors, 794 (38.7%) presented with at least one TB risk factor and 74 (3.6%) had symptoms consistent with active TB disease. Three seniors (0.2%)–each presenting with at least one risk factor—were diagnosed with active TB. The project yielded 146 TB cases per 100,000 seniors screened; the cost per case detected was $4,897. Most workers supported ACF if additional resources and staff could be provided. Seniors appreciated the convenience of this integrated health service approach. Conclusions: Although the yield was lower than expected, ACF appeared feasible in Bayi. Targeting seniors with at least one known TB risk factor could help detect previously unidentified TB cases. However, similar projects in communities with a higher TB prevalence are needed to further evaluate the yield and required resources prior to implementation on a larger scale. Findings from our pilot project should be combined with data from these future ACF projects to improve TB screening criteria. [ABSTRACT FROM AUTHOR]

Background: Brucellosis is one of the most common zoonoses worldwide, causing direct losses to the livestock industry and threatening human health. Little is known about the status and factors affecting farmers’ private investment in the prevention and control of sheep brucellosis in China. Methodology/Principal findings: From April to October 2017, a cross-sectional, house-based study was conducted in 7 Chinese provinces. A total of 1037 households included in the study were analyzed. The average amount of private investment in the prevention and control of brucellosis was $0.73±0.54 per sheep. Multivariable analysis showed that factors facilitating private investment included older age of householder (OR = 1.07, 95%CI: 1.03–1.11), herd size >100 (OR = 2.49, 95%CI: 1.38–4.51), a higher percentage of income from sheep farming comparing to the total household income (OR = 1.14, 95%CI: 1.11–1.16), higher score of brucellosis knowledge (OR = 3.85, 95%CI: 1.40–10.51), actively learning related knowledge (OR = 2.98, 95%CI: 1.55–5.74), actively participating in related training courses (OR = 3.07, 95%CI: 1.52–6.18), care about other people’s attitudes (OR = 1.75, 95%CI: 1.35–2.28), concern about the health of neighbors’ livestock (OR = 1.75, 95%CI: 1.23–2.51). The analysis found a discouraging factor for private investment, supporting culling policy (OR = 0.67, 95%CI: 0.49–0.91). Conclusions/Significance: In addition to providing interventions related to farmers’ knowledge, attitudes and practices, guidance must be offered to help farmers understanding the importance of private investment in the prevention and control of brucellosis. [ABSTRACT FROM AUTHOR]

Chinese jujube (Ziziphus jujuba), an economically important species in the Rhamnaceae family, is a popular fruit tree in Asia. Here, we surveyed and characterized simple sequence repeats (SSRs) in the jujube genome. A total of 436,676 SSR loci were identified, with an average distance of 0.93 Kb between the loci. A large proportion of the SSRs included mononucleotide, dinucleotide and trinucleotide repeat motifs, which accounted for 64.87%, 24.40%, and 8.74% of all repeats, respectively. Among the mononucleotide repeats, A/T was the most common, whereas AT/TA was the most common dinucleotide repeat. A total of 30,565 primer pairs were successfully designed and screened using a series of criteria. Moreover, 725 of 1,000 randomly selected primer pairs were effective among 6 cultivars, and 511 of these primer pairs were polymorphic. Sequencing the amplicons of two SSRs across three jujube cultivars revealed variations in the repeats. The transferability of jujube SSR primers proved that 35/64 SSRs could be transferred across family boundary. Using jujube SSR primers, clustering analysis results from 15 species were highly consistent with the Angiosperm Phylogeny Group (APGIII) System. The genome-wide characterization of SSRs in Chinese jujube is very valuable for whole-genome characterization and marker-assisted selection in jujube breeding. In addition, the transferability of jujube SSR primers could provide a solid foundation for their further utilization. [ABSTRACT FROM AUTHOR]