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Stress plays an important role in the etiology of schizophrenia. However, the mechanisms by which chronic physiological stress and perceived stress relate to the clinical features of schizophrenia may differ. We aimed to elucidate the relationships among chronic physiological stress indexed by allostatic load (AL), perceived stress, and clinical symptoms in individuals with first-episode schizophrenia (FES). Individuals with FES (n = 90, mean age = 28.26years old, 49%female) and healthy controls (111, 28.88, 51%) were recruited. We collected data of 13 biological indicators to calculate the AL index, assessed subjective stress with the Perceived Stress Scale-14 (PSS-14), and compared AL and perceived stress between groups. Patients with FES were also evaluated with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). Individuals with FES had higher AL and PSS score than healthy controls. There were no significant correlations between AL and PSS score in either patients or controls. Among individuals with FES, the AL index was associated with the severity of positive symptoms, while the PSS score was positively associated with CDSS score. Both elevated AL and PSS were correlated with the occurrence of schizophrenia. Physiological stress, as reflected by AL, may be more related to positive symptoms, while perceived stress appear to be associated with depressive symptoms in individuals with FES. Longitudinal studies are necessary to explore the relationships between interventions for different stressor types and specific clinical outcomes in FES. [ABSTRACT FROM AUTHOR]

• Klebsiella pneumoniae carbapenemase-producing Pseudomonas aeruginosa (KPC-PA) emerges. • A ST16 KPC-PA clone has not previously been reported. • Three-day levofloxacin treatment yielded resistance to imipenem-relebactam in KPC-PA. • Levofloxacin selected for a mexS mutation leading to cross resistance. Imipenem-relebactam (IMR), a novel β-lactam/β-lactamase inhibitor combination, is recommended for infections caused by difficult-to-treat Pseudomonas aeruginosa. This study aimed to investigate the evolution trajectory of IMR resistance under the selection of levofloxacin in P. aeruginosa. Antimicrobial susceptibility testing, complete genome sequencing and gene manipulation experiments were performed. Quantitative reverse transcription PCR for specific genes and porin levels were detected. Evolution trajectory was simulated in vitro by induction assay. P. aeruginosa HS347 and HS355 were isolated from abdominal drainage of two neighbouring patients (S and Z) undergoing surgery of colon carcinoma in Shanghai, China, with the latter patient having received levofloxacin. They were closely related ST16 strains, and both carried bla KPC-2 plasmids highly similar to those of P. aeruginosa endemic clones from Zhejiang province, where patient Z had received enteroscopy before this admission. Acquisition of resistance was observed for both IMR and fluoroquinolones in HS355, likely prompted by treatment with levofloxacin. The T274I substitution in MexS (putative oxidoreductase), upregulated efflux pump operon mexEF-oprN and decreased production of porin OprD leading to cross-resistance to fluoroquinolones and IMR, which was also verified by in vitro mutant selection under levofloxacin selection. The emergence of a rare bla KPC-2 -plasmid-bearing ST16 clone implies the horizonal spread and inter-regional dissemination of a high-risk plasmid-clone combination, representing a public health challenge. Levofloxacin exposure can select for mexS inactivating mutation, which in turn leads to IMR resistance phenotype, implicating the role of an unrelated, widely used antimicrobial agent in insidiously triggering the development of cross resistance to a latest β-lactam/β-lactamase inhibitor combination. Graphical abstract [Display omitted] [ABSTRACT FROM AUTHOR]

Physical parameters of existing building walls are relatively stable, making it difficult to meet the thermal requirements under different seasons. In this study, phase change materials (PCMs) with different thermal conductivities and melting points were adopted to form a breathable heterogeneous phase change material (B&H-PCM) wall to achieve the year-round heating and cooling load reduction. The effects of operation parameters on B&H-PCM and ventilated block (VB) wall were experimentally analyzed. As the hot air inlet temperature rose from 30 to 80 °C in winter, the heat storage capacity and liquefaction ratio continuously increased. The PCM heat storage rate was maximized at 50 °C with 26.7 %, and the liquefaction ratio of internal PCM was 100 % at 60 °C. As the air inlet velocity went up in winter/summer, the heat storage/dissipation capacity increased and the heat storage/dissipation rate changed oppositely. The maximum heat storage rate was 36 % at 0.5 m/s in winter, and the maximum heat dissipation rate was 58.7 % at 3 m/s in summer. The external/internal heat capacity and thermal resistance of B&H-PCM wall were 5.9/7.2 and 1.1/0.8 times of VB wall respectively, indicating that B&H-PCM wall had a better heat storage and resistance capacity both in winter and summer. • A breathable heterogeneous phase change material (B&H-PCM) wall was proposed. • The year-round wall thermal performance was experimentally analyzed and compared. • The wall external/internal heat capacity was improved by 5.9/7.2 times. • The wall external/internal thermal resistance was improved by 1.1/0.8 times. • B&H-PCM wall had better heat storage and resistance capacity in different seasons. [ABSTRACT FROM AUTHOR]

The B-cell lymphoma 2 (Bcl-2)-associated athanogene (BAG) family is a relatively conserved and multifunctional co-chaperones in animals and plants, which can flexibly interact with a variety of proteins and regulate various processes from growth and development to stress response. However, compared with animals, the function of BAG family in plant remains largely unknown, especially in response to cold stress. In this study, we have found that the expression of BAG8 was significantly induced in tomato under cold stress. Results showed that bag8 mutants exhibit significantly reduced tolerance towards cold stress, while BAG8 overexpressing lines were relatively resistant as reflected by the phenotype and membrane peroxidation. Measuring of gas exchange parameters, photosystem I (PSI) and photosystem II (PSII) of tomato leaves under cold stress further revealed that BAG8 mitigated cold-induced damage in photosynthetic system. Additionally, bag8 mutants exhibited more cold-induced reactive oxygen species, which were substantially normalized in BAG8 overexpressing plants. Nevertheless, the activities of antioxidant enzymes which were compromised in bag8 mutants were improved in BAG8 overexpressing plants facing cold stress. Additionally, BAG8 interacted with heat shock protein Hsp70 and protein phosphatase PP2A both in vitro and in vivo. Our results demonstrate that BAG8 plays a positive role in cold tolerance in tomato probably by the improvement of photosystems and antioxidant systems, and by interacting with Hsp70 involved in photosynthesis and PP2A involved in stomatal development. [Display omitted] • The expression of BAG8 is significantly induced in tomato under cold stress. • BAG8 positively regulates tomato cold tolerance as reflected by the phenotype and membrane peroxidation. • BAG8 mitigates cold-induced damage in photosynthetic system. • BAG8 can reduce oxidative damage by increasing the activities of antioxidant enzymes in plants facing cold stress. • BAG8 interactes with heat shock protein Hsp70 and protein phosphatase PP2A both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

The immune-inflammatory response system (IRS) and kynurenine pathway (KP) have been implicated in the pathophysiology of schizophrenia. Studies have shown inflammation-related effects on KP metabolism in patients with schizophrenia. This study investigated the relationship between KP metabolites, IRS, and the compensatory immune-regulatory reflex system (CIRS) in patients with treatment-resistant schizophrenia (TRS). Patients with (n = 53) and without TRS (n = 47), and healthy controls (HCs, n = 49) were enrolled. We quantified plasma levels of pro-inflammatory cytokines (interleukin [IL]-1β, IL-2, IL-6, soluble(s)IL-6 receptor, IL-8, IL-12, IL-17, IL-18, interferon-γ, and tumor necrosis factor[TNF]-α) and anti-inflammatory cytokines (IL-1 receptor antagonist, IL-4, IL-10, tumor growth factor [TGF]-β1, TGF-β2, soluble (s) IL-2 receptor subunit α, sIL-2 receptor subunit β, and sTNF-α receptor 1) and calculated the IRS/CIRS ratio. We also tested serum metabolites of the KP, including kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN), along with the QUIN/KYNA ratio. Patients with TRS had significantly higher IRS/CIRS ratio than non-TRS patients (p = 0.002) and HCs (p = 0.007), and significantly lower KYN (p = 0.001) and KYNA (p = 0.01) levels than HCs. Binary logistic regression analysis revealed that a younger age at illness onset (odds ratio [ OR ] = 0.91, p = 0.02) and a higher IRS/CIRS ratio (OR = 1.22; p = 0.007) were risk factors for patients with TRS. After further adjusted for age of onset, the QUIN/KYNA ratio (β = 0.97; p = 0.02) significantly moderated the relationship between IRS/CIRS and TRS, showing that in the higher QUIN/KYNA condition, higher IRS/CIRS ratio were significantly and more likely to be associated with patients with TRS (β = 0.12, z = 3.19, p = 0.001), whereas in the low QUIN/KYNA condition, the association between IRS/CIRS ratio and TRS was weak and insignificant. The peripheral immune response was imbalanced in TRS and was preferentially directed towards the IRS compared to patients without TRS and healthy controls, which is likely to play a role in neurotoxicity. Additionally, peripheral KP activation was also imbalanced, as evidenced by significantly reduced KYN and KYNA levels in patients with TRS compared to healthy controls, but none of KP metabolisms were significantly difference in non-TRS patients compared to healthy controls. QUIN/KYNA ratio involving to the degree of activation of NMDA receptors, indicated the neurotoxic level of the KP activation. The interaction between IRS/CIRS and QUIN/KYNA ratio was significant in predicting TRS, and our findings suggest a potential role for the immune-kynurenine pathway in TRS pathogenesis. • Patients with TRS showed significantly higher IRS/CIRS ratio than that in non-TRS patients and health controls. • The TRS group had a significant reduction in KYN and KYNA levels compared to healthy controls. • The IRS/CIRS ratio was a risk factor for TRS, while the age at onset of schizophrenia was a protective factor. • Controlling for the age of onset, elevated IRS/CIRS ratio was more likely to contribute to TRS in high QUIN/KYNA conditions. [ABSTRACT FROM AUTHOR]