Tryptophan residue of plasmid-encoded Pgp3 is important for Chlamydia muridarum to induce hydrosalpinx in mice

The crucial role of plasmid-encoded protein Pgp3 in Chlamydia pathogenesis has been demonstrated in various animal models. Previous studies have revealed that the Pgp3-deficient C. muridarum mutant fails to induce hydrosalpinx after vaginal inoculation in mice. Structural analysis of C. trachomatis Pgp3 trimer has indicated that Trp234 may play a critical role in trimeric crystal packing interactions and that Tyr197 is involved at predominant cation-binding sites. In this study, we constructed C. muridarum transformants harboring Pgp3, Trp234, or Tyr197 point mutations (Pgp3W234A and Pgp3Y197A). C3H/HeJ mice infected with Pgp3W234A mutant failed to induce severe hydrosalpinx in the oviduct tissue, which largely phenocopied the full-length Pgp3-deficient C. muridarum. The Pgp3Y197A variant induced an intermediate severity of pathology. The attenuated pathogenicity caused by the Pgp3W234A mutant may be due to its decreased survival in the lower genital tracts of mice, reduced ascension to the oviduct, and milder induction of inflammatory cell infiltration in the oviduct tissue. Thus, our results point to an important amino acid residue involved in Pgp3 virulence, providing a potential therapeutic target for chlamydial infection

The Structural Integrity of Plasmid-Encoded Pgp3 Is Essential for Induction of Hydrosalpinx by Chlamydia muridarum

Pgp3 consists of globular N- and C-terminal domains connected by a triple-helical coiled-coil middle domain. We demonstrated previously that Pgp3 is required for induction of hydrosalpinx by Chlamydia muridarum. We constructed C. muridarum transformants harboring deletion of the Pgp3 N-terminus (pgp3Δn), C-terminus (pgp3Δc), or middle domain (pgp3Δm). C3H/HeJ and CBA/J mice infected with pgp3Δn or pgp3Δm failed to induce hydrosalpinx in oviduct tissue. However, the pgp3Δc transformant induced mild hydrosalpinx in 20% of C3H/HeJ mice (severity score 0.2 ± 0.6) and in 40% of CBA/J mice (severity score 0.8 ± 1.3). The attenuated pathogenicity of the transformants harboring Pgp3 domain deletions was correlated with impaired in vitro growth and significantly reduced infectivity in the mouse lower genital tract. Moreover, the oviduct tissue of C3H/HeJ and CBA/J mice infected with the Pgp3-domain-deficient transformants displayed less inflammatory cell infiltration. Thus, the structural integrity of plasmid-encoded Pgp3 is essential for induction of hydrosalpinx by C. muridarum

Wield the Power of Omni-channel Retailing Strategy: a Capability and Supply Chain Resilience Perspective

Omni-channel strategy can be a powerful mechanism through which successful implementing organisations achieve higher levels of resilience to better survive disruptions. However, such potential benefits have been overlooked in existing literature with limited discussions on how omni-channel strategy can be exploited for uncertain business environments. We conduct an in-depth case study on a leading UK-based fashion retailer, Next, to explore the role of omni-channel strategy in helping organisations respond to the challenging retail landscape. Our results reveal that Next’s ability to achieve vitality even during the COVID-19 pandemic is largely attributed to its well-executed omni-channel strategy which enhances its supply chain resilience (SCRES) by maintaining a dynamic fit between the internal information processing capacity and the changing information processing needs induced by external conditions. Our study contributes to the omni-channel and SCRES literature and provides practical insights on how omni-channel strategy can be wielded for both stable and turbulent environments

Improving Seq2Seq Grammatical Error Correction via Decoding Interventions

The sequence-to-sequence (Seq2Seq) approach has recently been widely used in grammatical error correction (GEC) and shows promising performance. However, the Seq2Seq GEC approach still suffers from two issues. First, a Seq2Seq GEC model can only be trained on parallel data, which, in GEC task, is often noisy and limited in quantity. Second, the decoder of a Seq2Seq GEC model lacks an explicit awareness of the correctness of the token being generated. In this paper, we propose a unified decoding intervention framework that employs an external critic to assess the appropriateness of the token to be generated incrementally, and then dynamically influence the choice of the next token. We discover and investigate two types of critics: a pre-trained left-to-right language model critic and an incremental target-side grammatical error detector critic. Through extensive experiments on English and Chinese datasets, our framework consistently outperforms strong baselines and achieves results competitive with state-of-the-art methods.Comment: Accept to Findings of EMNLP 202

Thermo-economic evaluation and optimization of solar-driven power-to-chemical systems with thermal, electricity, and chemical storage

This paper evaluates the thermo-economics of power-to-chemicals using solar energy, with the chemicals being methane, methanol, and gasoline. In addition to the optimal technology sizing and heat cascade utilization, this paper also considers the optimal molten-salt solar power tower (MSPT) design, as the MSPT significantly affects the levelized product cost. A bi-level optimization is proposed, employing mixed-integer linear programming at the lower level with heat and mass integration for optimizing sizes and operating strategies of technologies, and with heat cascade utilization and a genetic algorithm at the upper level for optimizing the MSPT design. In the upper level, the full-load storage hours, design direct normal irradiance, solar multiple, and sizes of the MSPT are optimized. The electricity sources considered are the MSPT, photovoltaic (PV) with daily electricity storage, and the electrical grid as a complementary technology to satisfy the targeted daily product demand. Cost-competitiveness of solar-driven chemical synthesis is thoroughly assessed via considering sensitivity analysis on 1) regional solar resource endowments and actual local demands; 2) electricity sources, that is, PV vs. MSPT; and 3) the scale effect represented by different chemicals’ yield. The results show that the levelized methane cost ranges from 4.5 to 8.5 €/kg, depending on the location, plant size, and annual power contribution of concentrated solar power. Due to the larger mass production, the levelized cost of methanol and gasoline is lower: 1.5–2.2 €/kg for methanol and 4–6 €/kg for gasoline. The findings highlight the significance of location choice, that is, natural endowment of solar radiation and carbon sources. Using the syngas co-electrolysis pathway and direct solar radiation 100 kWh/m2 higher, the methane production cost is decreased by 2.4 €/kg. Sensitivity analysis performed on plant scale reveals that a compact, small-scale system is far too expensive. The levelized cost of methane could be decreased by 1.2 €/kg when the plant is scaled up from 4,000 to 20,000 kg/day H2. Due to its expensive electricity storage and limited working hours, PV is typically not chosen as a power source. Overall, solar fuels are unlikely to be cost-competitive in the near future when compared to market prices for all three compounds under consideration

Neuroendocrine pathogenesis of perimenopausal depression

With the development of social economics and the increase of working pressure, more and more women are suffering from long-term serious stress and showing symptoms of perimenopausal depression (PMD). The incidence rate of PMD is increasing, and the physical and mental health are seriously affected. However, due to the lack of accurate knowledge of pathophysiology, its diagnosis and treatment cannot be accurately executed. By consulting the relevant literature in recent years, this paper elaborates the neuroendocrine mechanism of perimenopausal depression from the aspects of epigenetic changes, monoamine neurotransmitter and receptor hypothesis, glial cell-induced neuroinflammation, estrogen receptor, interaction between HPA axis and HPG axis, and micro-organism-brain gut axis. The purpose is to probe into new ways of treatment of PMD by providing new knowledge about the neuroendocrine mechanism and treatment of PMD

Impacts of climate change on climatically suitable regions of two invasive Erigeron weeds in China

IntroductionErigeron philadelphicus and Erigeron annuus are two ecologically destructive invasive plants from the Asteraceae family. Predicting the potential distribution pattern of two invasive alien Erigeron weeds can provide a scientific basis for prevent the further spread of these two weeds in China under climate change.MethodsBased on historical occurrence datasets and environmental variables, we optimized a MaxEnt model to predict the potential suitable habitats of E. philadelphicus and E. annuus. We also analyzed the shifts of distribution centroids and patterns under climate change scenarios.ResultsThe key variables that affect the potential geographical distribution of E. annuus and E. philadelphicus, respectively, are temperature seasonality and precipitation of the driest month. Moreover, topsoil sodicity and topsoil salinity also influence the distribution of E. philadelphicus. Under climate change, the overall suitable habitats for both invasive alien Erigeron weeds are expected to expand. The potential geographical distribution of E. annuus exhibited the highest expansion under the SSP245 climate scenario (medium forcing scenarios), whereas E. philadelphicus had the highest expansion under the SSP126 climate scenario (lower forcing scenarios) globally. The future centroid of E. annuus is projected to shift to higher latitudes specifically from Hubei to Hebei, whereas E. philadelphicus remains concentrated primarily in Hubei Province. The overlapping suitable areas of the two invasive alien Erigeron plants mainly occur in Jiangsu, Zhejiang, Fujian, Jiangxi, Hunan, Guizhou, and Chongqing, within China.DiscussionClimate change will enable E. annuus to expand into northeastern region and invade Yunnan Province whereas E. philadelphicus was historically the only suitable species. E. annuus demonstrates a greater potential for invasion and expansion under climate change, as it exhibits higher environmental tolerance. The predictive results obtained in this study can serve as a valuable reference for early warning systems and management strategies aimed at controlling the spread of these two invasive plants