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Most knowledge regarding the effects of antidepressant drugs is at the receptor level, distal from the nervous system effects that mediate their clinical efficacy. Using functional magnetic resonance imaging (fMRI), this study investigated the effects of escitalopram, a selective serotonin reuptake inhibitor (SSRI), on resting-state brain function in patients with major depressive disorder (MDD). Fourteen first-episode drug-naive MDD patients completed two fMRI scans before and after 8 weeks of escitalopram therapy. Scans were also acquired in 14 matched healthy subjects. Data were analyzed using the regional homogeneity (ReHo) approach. Compared to controls, MDD patients before treatment demonstrated decreased ReHo in the frontal (right superior frontal gyrus), temporal (left middle and right inferior temporal gyri), parietal (right precuneus) and occipital (left superior occipital gyrus and right cuneus) cortices, and increased ReHo in the left dorsal medial prefrontal gyrus and left anterior lobe of the cerebellum. Compared to the unmedicated state, ReHo in the patients after treatment was decreased in the left dorsal medial prefrontal gyrus, the right insula and the bilateral thalamus, and increased in the right superior frontal gyrus. Compared to controls, patients after treatment displayed a ReHo decrease in the right precuneus and a ReHo increase in the left anterior lobe of the cerebellum. Successful treatment with escitalopram may be associated with modulation of resting-state brain activity in regions within the fronto-limbic circuit. This study provides new insight into the effects of antidepressants on functional brain systems in MDD.

IntroductionPrevious Electronic Health Records (EHR) based studies adopted various definitions in identifying Treatment-Resistant Depression (TRD) patients. There is a lack of similar attempts among Chinese population which limits the understanding of TRD in China.ObjectivesAssess TRD identification using EHR from a major psychiatric hospital in China.MethodsThis study utilized a retrospective Major Depressive Disorder (MDD) cohort of patients who newly initiated pharmaceutical treatment (2010-2018); follow-up was ended upon 1-year or treatment discontinuation (≥120d without treatment). TRD was first identified based on common clinical definition of two prior regimen failures (change of regimen) with 4-week as regimen adequacy threshold (Def1). Alternative adequacy thresholds of 2-week and 6-week were applied. Based on Def1 (4-week), at least 3 distinctive regimens were additionally required in TRD identification (Def2). Further, a data-driven definition (Def3) based on drug count as having ≥3 antidepressants or ≥1 antipsychotic within 1 year was considered (Cepeda et al., 2018).ResultsFrom 12257 MDD patients included in the cohort, Def1 identified 633 (5.2%) TRD cases, whereas regimen adequacy thresholds of 2-week and 6-week identified 1772 (14.5%) and 61 (0.5%) cases, respectively. Further, Def2 identified 261 (2.4%) TRD cases. Finally, Def3 yielded 2449 (20.0%) TRD cases, including 1966 exclusive cases that were not identified by Def1.ConclusionsThis study showed different definitions for TRD identification had considerable impact on the number of patients identified among Chinese population, obscuring the comparability among EHR-based TRD studies. As first step, we found the criteria of regimen adequacy as major contributor to the observed variability in China.DisclosureNo significant relationships.

The effects of NaCl and Na 2 SO 4 on photosynthetic pigments, malondialdehyde (MDA), Rubisco activity and superoxide dismutase (SOD) activity were investigated in Kalidium foliatum (Pall.) Moq., which is distributed in the saline soil of Hetao irrigation area in Inner Mongolia China. The K. foliatum plants were treated with NaCl (0, 100, 250, 400 and 500 mM), Na 2 SO 4 (0, 100, 250, 400 and 500 mM) and NaCl + Na 2 SO 4 (1: 1, v/v) (0, 100, 250, 400 and 500 mM of Na + concentration, 0, 50, 125, 200 and 250 mM of Cl – and SO 4 2– concentration) for 10 days. Content of chlorophylls and carotenoids were significantly higher than control at increasing NaCl and Na 2 SO 4 concentration, in contrast, were significantly reduced by higher concentration of NaCl + Na 2 SO 4 . Rubisco activity reduced steadily at 100 and 250 mM NaCl, while increased at 400 and 500 mM NaCl. Rubisco activity was significantly higher than control at 100 mM Na 2 SO 4 , and was no more change under NaCl + Na 2 SO 4 treatment. The SOD activity increased with increasing NaCl and Na 2 SO 4 , and increased at moderate NaCl + Na 2 SO 4 treatment. MDA content was lower than control at 250 mM salt concentration. On the basis of the data obtained, K. foliatum showed resistance to salt such as Na + , Cl – and SO 4 2– , Rubisco activity in K. foliatum might be more sensitive to salt.

Viruses evolve in infected host populations, and host population dynamics affect viral evolution. RNA viruses with a short duration of infection and a high peak viral load, such as SARS-CoV-2, are maintained in human populations. By contrast, RNA viruses characterized by a long infection duration and a low peak viral load (e.g., borna disease virus) can be maintained in nonhuman populations, and the process of the evolution of persistent viruses has rarely been explored. Here, using a multi-level modeling approach including both individual-level virus infection dynamics and population-scale transmission, we consider virus evolution based on the host environment, specifically, the effect of the contact history of infected hosts. We found that, with a highly dense contact history, viruses with a high virus production rate but low accuracy are likely to be optimal, resulting in a short infectious period with a high peak viral load. In contrast, with a low-density contact history, viral evolution is toward low virus production but high accuracy, resulting in long infection durations with low peak viral load. Our study sheds light on the origin of persistent viruses and why acute viral infections but not persistent virus infection tends to prevail in human society.

Abstract An extension of the two Higgs doublet model including inverse seesaw neutrinos and neutral Higgs bosons was constructed based on the A4 symmetry in order to explain the recent neutrino oscillation data. This model can distinguish two well-known normal and inverted order schemes of neutrino data once both the effective masses mβ in tritium beta decays and 〈m〉 in the neutrinoless double beta decay are observed. The lepton flavor violating decays of the charged leptons eb → eaγ, μ → 3e, the Standard Model-like Higgs boson decays h → ebea, and the μ–e conversions in some nuclei are generated from loop corrections. The experimental data on the branching ratio Br(μ → eγ, 3e) predict that the upper bounds of Br(τ → μγ, eγ) and Br(h → eaeb) are much smaller than the planned experimental sensitivities. In contrast, the μ–e conversions are promising signals for experiments.

Nectin-3, a cell adhesion molecule enriched in hippocampal neurons, has been implicated in stress-related cognitive disorders. Nectin-3 is expressed by granule cells in the dentate gyrus (DG), but it remains unclear whether nectin-3 in DG modulates the structural plasticity of dentate granule cells and hippocampus-dependent memory. In this study, we found that DG nectin-3 expression levels were developmentally regulated and reduced by early postnatal stress exposure in adult mice. Most importantly, knockdown of nectin-3 levels in all DG neuron populations by adeno-associated virus (AAV) mimicked the cognitive effects of early-life stress, and impaired long-term spatial memory and temporal order memory. Moreover, AAV-mediated DG nectin-3 knockdown increased the density of doublecortin-immunoreactive differentiating cells under proliferation and calretinin-immunoreactive immature neurons, but markedly decreased calbindin immunoreactivity, indicating that nectin-3 modulates the differentiation and maturation of adult-born DG granule cells. Using retrovirus to target newly generated DG neurons, we found that selective nectin-3 knockdown in new DG neurons also impaired long-term spatial memory. In addition, suppressing nectin-3 expression in new DG neurons evoked a reduction of dendritic spines, especially thin spines. Our data indicate that nectin-3 expressed in DG neurons may modulate adult neurogenesis, dendritic spine plasticity and the cognitive effects of early-life stress.

A number of studies have indicated that 8p22–p12 is likely to harbor schizophrenia susceptibility loci. In this region, the candidate gene of interest, neuregulin 1 (NRG1), may play a role in the pathogenesis of schizophrenia. Then in the present study, we performed the linkage disequilibrium to determine the association between three genetic variants (SNPs: rs3924999, rs2954041, SNP8NRG221533) on NRG1 gene and schizophrenia in 246 Chinese Han schizophrenic family trios using PCR-based restriction fragment length polymorphism method and denaturing high-performance liquid chromatography. The transmission disequilibrium test analysis for each variant showed a significant difference between two transmitted alleles even after Bonferroni correction (rs3924999, P =0.007752; rs2954041, P =0.0009309; SNP8NRG221533, P =0.012606). The global χ 2 test for haplotype transmission also revealed a strong association (χ 2 =46.068, df=7, P <0.000001). Our results suggest that the NRG1 gene may play a role in conferring susceptibility to the disease.

In recent years, underground spaces have expanded widely in the urban zone. The appropriate estimation number of dewatering well with economical costs and securing soil stability at construction sites is challenging in designing pumping schemes. This paper aims to present the numerical approach for the optimal number of wells for designing a dewatering deep foundation pit. First, the estimated hydraulic conductivity was selected among the Theis, Cooper-Jacod, and reverse groundwater modeling methods. The estimated hydraulic conductivity via reverse groundwater modeling shows the lowest error with the monitoring pumping test. Second, hydraulic conductivity was input to groundwater modeling to estimate the groundwater level of four pumping schemes with the same total pumping rate (20 wells, 17 wells, 14 wells, and 13 wells). The number of wells was optimal from four random pumping schemes concerning the cost and the drawdown outside the pit. As a result, the pumping scheme with 16 wells is suitable, satisfying the cost and safety outside the drawdown of the foundation pit. The numerical approach could apply to estimate the number of wells for dewatering projects with economic costs and less impact on surrounding construction sites.

A set of 224 recombinant inbred lines (RILs) derived from a narrow cross between two fresh eaten types (S94 (Northern China type) x S06 (Northern European type)) (Cucumis sativus L.) was used to construct a genetic linkage map. With the RILs a 257-point genetic map was constructed including 206 SRAPs, 22 SSRs, 25 SCARs, 1 STS, and three economically important morphological markers (small spines (ss), uniform immature fruit color (u), dull fruit skin (D)). The seven linkage groups covered 1005.9 cM with a mean marker interval of 3.9 cM. The ss locus was linked to D and u, and they were all on Linkage group 6. The RIL map contained a total of 51 sequence-specific markers, which made possible the comparison of molecular linkage maps developed in different laboratories. Using the F₆:₇ derived families, a total of 78 QTLs were detected with relatively high LOD scores (2.9-84.4) for nine fruit-related traits (fruit weight, length, and diameter, fruit flesh thickness, seed-cavity diameter, fruit-stalk length, fruit pedicel length, length/diameter and length/stalk ratio) and three flower-related traits (first flower node, first female flower node and female flower ratios). Several sequence-anchor markers (CSWCT25, CS30, CMBR41, CS08 etc.) were closely linked with some QTLs for fruit weight, fruit length, fruit flesh thickness and sex expression, which can be used for the future marker-assisted selection to improve the fruit traits in cucumber breeding.

Linezolid is an antibiotic of last resort for the treatment of infections caused by Gram-positive bacteria, including vancomycin-resistant enterococci. Enterococcus faecalis, a member of enterococci, is a significant pathogen in nosocomial infections. E. faecalis resistance to linezolid is frequently related to the presence of optrA, which is often co-carried with fex, phenicol exporter genes, and erm genes encoding macrolide resistance. Therefore, the common use of antibiotics in veterinary might promote the occurrence of optrA in livestock settings. This is a cross-sectional study aiming to investigate the prevalence of optrA positive E. faecalis (OPEfs) in 6 reservoirs in farms in Ha Nam province, Vietnam, and its associated factors and to explore genetic relationships of OPEfs isolates. Among 639 collected samples, the prevalence of OPEfs was highest in flies, 46.8% (51/109), followed by chickens 37.3% (72/193), dogs 33.3% (17/51), humans 18.7% (26/139), wastewater 16.4% (11/67) and pigs 11.3%, (14/80). The total feeding area and total livestock unit of the farm were associated with the presence of OPEfs in chickens, flies, and wastewater. Among 186 OPEfs strains, 86% were resistant to linezolid. The presence of optrA was also related to the resistant phenotype against linezolid and levofloxacin of E. faecalis isolates. Close genotypic relationships identified by Pulsed Field Gel Electrophoresis between OPEfs isolates recovered from flies and other reservoirs including chickens, pigs, dogs, and wastewater suggested the role of flies in the transmission of antibiotic-resistant pathogens. These results provided warnings of linezolid resistance although it is not used in livestock.