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Wintertime deepwater renewal, which is important for heat–oxygen–nutrient exchange in lakes, is traditionally considered to be mainly driven by 1D vertical convective cooling. However, differential cooling between shallow and deep waters can produce density currents that flow into deep layers. In order to determine the role that these two cooling processes play in deepwater renewal, field measurements and 3D numerical modeling were combined to investigate heat content dynamics in Lake Geneva's large basin, the Grand Lac (maximum depth 309 m), during an exceptionally cold air spell in early 2012 where complete overturning had been reported. In a novel approach, the heat budget of the lake was decomposed, which allowed the identification and quantification of the heat budget components. The heat budget decomposition revealed that vertical convective cooling only penetrated to 200 m and that lateral advection was not only caused by density currents being discharged from the shallow littoral zone of the Grand Lac, but also from the Lake's shallow Petit Lac basin (maximum depth 75 m); the latter was found to be the main driver of heat content decrease in the deep layers of the Grand Lac below ∼200‐m depth. These findings provide unique insight into heat exchange processes that cannot be obtained from field data or numerical simulations alone. Heat budget decomposition proved to be a powerful, universally applicable tool for quantifying the contribution of alternative deepwater renewal processes. This is important, since deepwater renewal by convective cooling is weakening due to persistent global warming. Plain Language Summary: Winter cooling is an important process for heat–oxygen–nutrient exchange in lakes. Traditionally considered to be mainly driven by 1D vertical convective cooling, complete overturning occurs when temperatures become homogeneous over the full water depth. In most deep lakes, this only occurs occasionally. Complete overturning in 309‐m deep Lake Geneva was reported for winter 2012. Field measurements taken at the deepest part of the lake, however, showed that the lake's temperature profile during that winter was not uniform. Instead, it had a cooler, deep bottom layer. To understand this temperature profile, we used 3D numerical modeling to decompose the lake's heat budget. This novel approach made it possible to investigate and quantify the contribution of: (a) vertical top‐down convective cooling, and (b) lateral advection of cold water from shallower regions to the lake's deep layers. The results revealed that convective cooling did not reach below ∼200‐m depth. Instead, lateral cold‐water advection from the lake's shallow side basin and nearshore regions were responsible for the cooling and deepwater renewal below that depth. As climate change induced‐warming continues to weaken convective cooling, it will become increasingly important to understand and consider lateral advection as an alternative deepwater renewal process in large, deep lakes. Key Points: Deepwater renewal in a large, 309‐m deep lake during a very cold air spell is investigated by field observations and 3D numerical modelingA novel heat budget decomposition methodology allows for quantification of contributions of different processes to deepwater renewalLateral advection by density currents from shallow areas and a side basin was identified as the governing process in deepwater renewal [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Lin et al papers. To view these articles visit https://doi.org/10.1111/apt.13774 and https://doi.org/10.1111/apt.13849. [ABSTRACT FROM AUTHOR]

Aims Endothelium-derived protein disulphide isomerase (PDI) is required for thrombus formation in vivo. But, how to control PDI overproduction in oxidized low-density lipoprotein (oxLDL)-activated vascular endothelial cells (VECs) is not well understood. In this study, we try to answer this question using our newly identified activator of mTOC1 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2 (3H)-one (3BDO) that has been shown to protect VECs. Methods First, we performed a proteomics analysis on the ox LDL-activated vascular VECs in the presence or absence of 3 BDO. Next, we constructed the heterogeneous nuclear ribonucleoprotein E1 (hn RNP E1) mutants at Ser43 and used the RNA-Ch IP technique to investigate the relationship between hn RNP E1 and PDI production. Furthermore, we examined the effect of 3 BDO on ox LDL-altered phosphorylation of Akt1 and Akt2. Finally, we studied the effect of 3 BDO on ox LDL-altered PDI protein level in apolipoprotein E−/− mice with advanced atherosclerosis. Results In VECs, ox LDL-increased PDI protein level, induced hn RNP E1 phosphorylation at Ser43, suppressed the binding of hn RNP E1 to PDI 5′ UTR and induced the phosphorylation of Akt2 but not Akt1. All of these processes were blocked by 3 BDO. Importantly, Ser43 mutant of hn RNP E1 inhibited the increase of PDI protein level and the decrease of the binding of hn RNP E1 and PDI 5′ UTR induced by ox LDL. Furthermore, 3 BDO suppressed ox LDL-induced PDI protein increase in the serum and plaque endothelium of apolipoprotein E−/− mice. Conclusion hn RNP E1 is a new regulator of PDI translation in ox LDL-activated VECs, and 3 BDO is a powerful agent for controlling PDI overproduction. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the study regarding the efficacy of oral nucleos(t)ide analogue therapy in patients with hepatitis B virus-related hepatocellular carcinoma (HCC) by G. L. Wong and colleagues in the 2016 issue.

Background  A standard third-line therapy for Helicobacter pylori infection is lacking, and antimicrobial sensitivity data for patients who failed eradication therapy are often unavailable in clinical practice. We therefore designed the prospective study to assess the efficacy of levofloxacin, amoxicillin, bismuth and rabeprazole quadruple therapy as a third-line treatment for H. pylori infection. Patients and methods  From September 2005 to August 2007, 37 consecutive H. pylori-infected patients who had failed standard first-line and second-line treatments underwent a 10-day quadruple therapy comprising rabeprazole (20 mg b.i.d.), bismuth subcitrate (300 mg q.d.s.), amoxicillin (500 mg q.d.s.) and levofloxacin (500 mg o.d.). Follow-up endoscopy with rapid urease test, histological examination and culture was performed at 6 weeks after the end of treatment to evaluate the response to therapy. Results  Helicobacter pylori was successfully eradicated in 31 out of 37 patients (84% by both intention-to-treat analysis and per-protocol analysis). All patients complied with the eradication therapies, and only seven patients (19%) complained of mild-to-moderate adverse events. Amoxicillin- and levofloxacin-resistant strains were observed in 17% and 22% of the patients, respectively. There were no significant differences between H. pylori eradication rates and antibiotic resistances. Conclusions  The 10-day levofloxacin- and amoxicillin-based quadruple therapy is well tolerated and achieves a high eradication rate as a third-line empirical treatment for H. pylori infection. [ABSTRACT FROM AUTHOR]

Background This prospective, randomized, controlled study was conducted to compare the efficacies of high-dose and low-dose esomeprazole-based triple therapies for Helicobacter pylori eradication in Taiwan. Materials and methods From January 2004 to June 2006, 240 H. pylori-infected patients were randomly assigned to undergo high-dose (40 mg b.d.) or low-dose (40 mg o.d.) esomeprazole combined with clarithromycin (500 mg b.d.) and amoxicillin (1 g b.d.) for one week. Follow-up endoscopy was performed at eight weeks after the end of treatment to evaluate the response to therapy. Results Intention-to-treat analysis demonstrated no differences between eradication rates of high-dose and low-dose groups (92% vs. 90%, respectively, P > 0·05). Per-protocol analysis yielded comparable results (95% vs. 93%). Both groups exhibited similar frequencies of adverse events (13% vs. 11%) and drug compliance (96% vs. 93%). Multivariate analysis indicated that only good compliance (odds ratio: 10·3, 95% CI, 3·0–35·7) was an independent predictor of treatment success. Conclusions This work demonstrates that low-dose esomeprazole-based triple therapy yields a similar eradication rate as high-dose esomeprazole-based therapy in Taiwan. Since the cost of the low-dose regime is lower than that of the high-dose regime, low-dose esomeprazole-based triple therapy can reasonably be recommended for the first-line eradication of H. pylori for Taiwanese and probably most Asians. [ABSTRACT FROM AUTHOR]

Background: Although the eradication of Helicobacter pylori infection benefits patients with gastric or duodenal ulcers, the value of eradicating the infection in the patients with functional dyspepsia (FD) remains controversial. Aims: To determine whether eradicating H. pylori can prevent the subsequent development of ulcers or relieve the symptoms of functional dyspepsia patients. Methods: In a double-blind, placebo-controlled trial, 161 patients infected with H. pylori who had functional dyspepsia were randomly assigned to 7 days of treatment with a lansoprazole-based triple therapy or placebo and then followed for 1 year. The main outcome measures were the development of peptic ulcers and the resolution of symptoms. Results: H. pylori was eradicated in 63 out of 81 patients (78%) in the treatment group and none of the 80 patients (0%) in the placebo group. During the follow-up period, two patients in the treatment group and six patients in the placebo group developed peptic ulcers at repeat endoscopy (2.5% vs. 7.5%; 95% CI: –12 to 2). The reduction in ulcer rates was statistically significant in the ‘ulcer-like’ sub-group (0% vs. 16.7%; 95% CI: –32 to –2), but not in the ‘dysmotility-like’ and ‘unclassifiable’ sub-groups. Regarding symptom response, the resolution rates of symptoms were similar between the treatment and placebo groups (58.0% vs. 55.0%, 95% CI: –12 to 18). Additionally, no significant differences existed in the symptom responses between the treatment and control arms in each of the dyspepsia sub-groups. Conclusions: Eradicating H. pylori can prevent the subsequent development of peptic ulcers in the patients with ‘ulcer-like’ functional dyspepsia. However, this approach does not significantly reduce the symptoms of functional dyspepsia patients. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Bock et al and Bantel et al papers. To view these articles visit https://doi.org/10.1111/apt.13578 and https://doi.org/10.1111/apt.13826. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC), a very aggressive tumour, is currently the third leading cause of cancer-related deaths. Unfortunately, many patients face the issue of inoperability at the diagnostic phase leading to a quite dismal prognosis. The onset of metastatic processes has a crucial role in the elevated mortality rates linked to PDAC. Individuals with metastatic advances receive only palliative therapy and have a grim prognosis. It is essential to carefully analyse the intricacies of the metastatic process to enhance the prognosis for individuals with PDAC. Malignancy development is greatly impacted by the process of macrophage efferocytosis. Our current knowledge about the complete range of macrophage efferocytosis activities in PDAC and their intricate interactions with tumour cells is still restricted. This work aims to resolve communication gaps and pinpoint the essential transcription factor that is vital in the immunological response of macrophage populations. We analysed eight PDAC tissue samples sourced from the gene expression omnibus. We utilized several software packages such as Seurat, DoubletFinder, Harmony, Pi, GSVA, CellChat and Monocle from R software together with pySCENIC from Python, to analyse the single-cell RNA sequencing (scRNA-seq) data collected from the PDAC samples. This study involved the analysis of a comprehensive sample of 22,124 cells, which were classified into distinct cell types. These cell types encompassed endothelial and epithelial cells, PDAC cells, as well as various immune cells, including CD4+ T cells, CD8+ T cells, NK cells, B cells, plasma cells, mast cells, monocytes, DC cells and different subtypes of macrophages, namely C0 macrophage TGM2+, C1 macrophage PFN1+, C2 macrophage GAS6+ and C3 macrophage APOC3+. The differentiation between tumour cells and epithelial cells was achieved by the implementation of CopyKat analysis, resulting in the detection and categorization of 1941 PDAC cells. The amplification/deletion patterns observed in PDAC cells on many chromosomes differ significantly from those observed in epithelial cells. The study of Pseudotime Trajectories demonstrated that the C0 macrophage subtype expressing TGM2+ had the lowest level of differentiation. Additionally, the examination of gene set scores related to efferocytosis suggested that this subtype displayed higher activity during the efferocytosis process compared to other subtypes. The most active transcription factors for each macrophage subtype were identified as BACH1, NFE2, TEAD4 and ARID3A. In conclusion, the examination of human PDAC tissue samples using immunofluorescence analysis demonstrated the co-localization of CD68 and CD11b within regions exhibiting the presence of keratin (KRT) and alpha-smooth muscle actin (α-SMA). This observation implies a spatial association between macrophages, fibroblasts, and epithelial cells. There is variation in the expression of efferocytosis-associated genes between C0 macrophage TGM2+ and other macrophage cell types. This observation implies that the diversity of macrophage cells might potentially influence the metastatic advancement of PDAC. Moreover, the central transcription factor of different macrophage subtypes offers a promising opportunity for targeted immunotherapy in the treatment of PDAC., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

As the COVID-19 variant Omicron surge in Beijing, China, a better understanding of risk factors for adverse outcomes may improve clinical management in patients with haematological malignancies (HM) diagnosed with COVID-19. The study sample includes 412 cases, mainly represented by acute leukaemia, chronic myeloid leukaemia (CML), plasma cell disorders and lymphoma and chronic lymphocytic leukaemia. COVID-19 pneumonia was observed in 10.4% (43/412) of patients, and severe/critical illness was observed in 5.3% (22/412). Among the 86 cases with advanced malignancies, 17.6% (12/86) of patients developed severe/critical COVID-19, which was significantly higher than reported in patients with stable malignancies (9/326, 2.70%, p < 0.001). Similarly, the advanced malignancy cohort had a higher mortality rate (9/86, 10.5% vs. 0/326, 0%, p < 0.001) and a poor 30-day overall survival (OS) compared with the stable malignancy cohort (74.2% vs. 100.0%, p < 0.0001). Overall, nine patients (2.2%) died. The primary cause of death was progressive HM in four patients and a combination of both COVID-19 and HM in five patients. In the multivariable analysis, over 65 years of age, comorbidities and advanced malignancy were correlated with severe/critical COVID-19 in HM patients. This study sheds light on the poor outcomes among COVID-19 HM patients with the leading cause of advanced malignancy., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Prostate cancer is the second most frequent malignancy in men worldwide, and its incidence is increasing. Therefore, it is urgently required to clarify the underlying mechanisms of prostate cancer. Although the long non-coding RNA LINC00115 was identified as an oncogene in several cancers, the expression and function of LINC00115 in prostate cancer have not been explored. Our results showed that LINC00115 was significantly up-regulated in prostate cancer tissues, which was significantly associated with a poor prognosis for prostate cancer patients. Functional studies showed that knockdown LINC00115 inhibited cell proliferation and invasion. In addition, LINC00115 served as a competing endogenous RNA (ceRNA) through sponging miR-212-5p to release Frizzled Family Receptor 5 (FZD5) expression. The expression of miR-212-5p was noticeably low in tumour tissues, and FZD5 expression level was down-regulated with the knockdown of LINC00115. Knockdown LINC00115 inhibited the Wnt/β-catenin signalling pathway by inhibiting the expression of FZD5. Rescue experiments further showed that LINC00115 inhibits prostate cancer cell proliferation and invasion via targeting miR-212-5p/ FZD5/ Wnt/β-catenin axis. The present study provided clues that LINC00115 may be a promising novel therapeutic target for prostate cancer patients., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

This study aimed to examine miR-140 expression in clinical samples from tuberculosis (TB) patients and to explore the molecular mechanisms of miR-140 in host-bacterial interactions during Mycobacterium tuberculosis (M tb) infections. The miR-140 expression and relevant mRNA expression were detected by quantitative real-time PCR (qRT-PCR); the protein expression levels were analysed by ELISA and western blot; M tb survival was measured by colony formation unit assay; potential interactions between miR-140 and the 3' untranslated region (UTR) of tumour necrosis factor receptor-associated factor 6 (TRAF6) was confirmed by luciferase reporter assay. MiR-140 was up-regulated in the human peripheral blood mononuclear cells (PBMCs) from TB patients and in THP-1 and U937 cells with M tb infection. Overexpression of miR-140 promoted M tb survival; on the other hand, miR-140 knockdown attenuated M tb survival. The pro-inflammatory cytokines including interleukin 6, tumour necrosis-α, interleukin-1β and interferon-γ were enhanced by M tb infection in THP-1 and U937 cells. MiR-140 overexpression reduced these pro-inflammatory cytokines levels in THP-1 and U937 cells with M tb infection; while knockdown of miR-140 exerted the opposite actions. TRAF6 was identified to be a downstream target of miR-140 and was negatively modulated by miR-140. TRAF6 overexpression increased the pro-inflammatory cytokines levels and partially restored the suppressive effects of miR-140 overexpression on pro-inflammatory cytokines levels in THP-1 and U937 cells with M tb infection. In conclusion, our results implied that miR-140 promoted M tb survival and reduced the pro-inflammatory cytokines levels in macrophages with M tb infection partially via modulating TRAF6 expression., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)