The correlation between the expression of ATF4 and procalcitonin combined with the detection of RET mutation and the pathological stage and clinical prognosis of medullary thyroid carcinoma.

To explore the correlation between the activating transcription factor 4 (ATF4) and procalcitonin (PCT) expressions combined with RET mutation and the pathological staging and clinical prognosis of sporadic medullary thyroid carcinoma (SMTC). Fifty cases (tumor tissue) of SMTC diagnosed by clinicopathology were collected and the patients with nodular goiter were selected as normal control. The RET mutation site was analyzed by detection kit and expressions of PCT and ATF4 in SMTC were analyzed by Western blot and immunohistochemistry. Multiple linear regression was used to analyze the correlation of risk factors (PCT or ATF4 expression, RET mutation, tumor differentiation, SMTC stage, lymphatic metastasis) for 5-year recurrence and survival of SMTC. The ATF4 and PCT expressions were significantly decreased and increased, respectively, with the increase of the SMTC stage. The most frequent mutation of RET gene in cancer tissue was M 22458A in exon 16. The ATF4 and PCT expressions, as well as RET mutation, were significantly associated with a 5-year recurrence, while the ATF4 expression was significantly related to better 5-year survival. ATF4 and PCT expressions combined with RET mutation are related to the clinical prognosis of SMTC and can predict SMTC staging.

Tumor infiltrating neutrophil might play a major role in predicting the clinical outcome of breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: This study was aimed to explore the predictive ability of tumor infiltrating neutrophil (TIN) in patients with breast cancer treated with neoadjuvant chemotherapy (NACT). Furthermore, the significance of TIN's dynamic change before and after NACT was investigated. METHODS: Between January 2004 and December 2017, a total of 133 patients with breast cancer who underwent NACT before surgery were enrolled in this retrospective cohort. Eighty-nine of them were able to get the core needle biopsy (CNB) samples and all the pathological samples after surgery were available. TIN was detected by immunohistochemical staining of CD66b. The optimal cut-off value was determined via receiver operating characteristic (ROC) curve analysis. The association of clinicopathologic characteristics and chemotherapy efficiency was analyzed using X2 test or Fisher's exact test or t-test as appropriate, and the prognostic significances were assessed by univariate and multivariate analyses. RESULTS: Patients with higher TIN after NACT were confirmed to be significantly associated with worse prognosis (P = 0.002). After stratifying patients into two groups, high difference group was prone to have better chemotherapy efficiency (P < 0.001) and clinical outcome in both univariate (P = 0.002) and multivariate analyses (P = 0.003). CONCLUSIONS: In this study, higher TIN after NACT was confirmed to be associated with breast cancer patients' worse chemotherapy efficiency and shorter disease-free survival (DFS). Furthermore, the TIN's dynamic change before and after NACT was firstly proved to be a more accurate predictive marker compared with TIN after NACT.

Paenibacillus tianjinensis sp. nov., isolated from corridor air.

A Gram-stain-positive, facultatively anaerobic, non-motile, endospore-forming and rod-shaped bacterium, occurring singly or in pairs, designated TB2019T, was isolated from environmental monitoring samples of corridor air collected at the Tianjin Institute for Drug Control, Tianjin Province (PR China). The isolate was able to grow at 15-40 °C (optimum growth at 37 °C), pH 6.0-8.0 (pH 7.0) and in the presence of 0-2% (w/v) NaCl (0% NaCl). Comparison of 16S rRNA gene sequences indicated that TB2019T was most closely related to Paenibacillus typhae CGMCC 1.11012T (98.63%), Paenibacillus albidus Q4-3T (98.19%), Paenibacillus borealis DSM 13188T (97.55%), Paenibacillus helianthi P26ET (97.33%) and Paenibacillus odorifer DSM 15391T (97.19%). The digital DNA-DNA hybridization and the average nucleotide identity values between TB2019T and the five type strains mentioned above ranged from 20.7 to 25.0% and 75.2 to 81.3%, respectively, and the genomic DNA G+C content was 49.52 mol%. The diagnostic cell-wall sugar was ribose, and the diagnostic amino acid was meso-diaminopimelic acid. The polar lipids of TB2019T included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, three unidentified aminophospholipids and one unidentified phospholipid. MK-7 was the predominant menaquinone, and anteiso-C15:0 (30.6%) was the major fatty acid. Based on the polyphasic taxonomic data, strain TB2019T represents a novel species of the genus Paenibacillus, for which the name Paenibacillus tianjinensis sp. nov. is proposed. The type strain is TB2019T (=CICC 25065T=JCM 34610T).

CKS1B promotes cell proliferation and invasion by activating STAT3/PD-L1 and phosphorylation of Akt signaling in papillary thyroid carcinoma.

OBJECTIVE: To investigate role of GKS1B and its relationship between STAT3/PD-L1 and p-Akt in papillary thyroid carcinoma (PTC). METHODS: Expression of GKS1B and PD-L1 was determined in PTC cell lines. GKS1B was overexpressed or knocked down by transfection with overexpression plasmids or si-CKS1B. STAT3 inhibitor WP1066 was used to suppress STAT3, and PD-L1 inhibitor Pembrolizumab was used to block PD-L1. Cell viability and invasion were evaluated by MTT and transwell assay, respectively. The expression of STAT3, p-STAT3, Akt, and p-Akt was measured using Western blotting. RESULTS: Both protein levels and mRNA levels of CKS1B and PD-L1 were remarkably up-regulated in PTC cell lines. Knockdown of CKS1B significantly inhibited cell viability and invasion of PTC cells and suppressed STAT3/PD-L1 signaling and Akt phosphorylation, while overexpression of CKS1B led to opposite results. Inhibition of STAT3 or PD-L1 reversed the effects of overexpressed CKS1B on PTC cells. CONCLUSION: The overexpression of CSK1B could promote cell viability and invasion of PTC cells through activation of STAT3/PD-L1 signaling and Akt phosphorylation.

Validation of SV2A-Targeted PET Imaging for Noninvasive Assessment of Neuroendocrine Differentiation in Prostate Cancer.

Neuroendocrine prostate cancer (NEPC) is an aggressive and lethal variant of prostate cancer (PCa), and it remains a diagnostic challenge. Herein we report our findings of using synaptic vesicle glycoprotein 2 isoform A (SV2A) as a promising marker for positron emission tomography (PET) imaging of neuroendocrine differentiation (NED). The bioinformatic analyses revealed an amplified SV2A gene expression in clinical samples of NEPC versus castration-resistant PCa with adenocarcinoma characteristics (CRPC-Adeno). Importantly, significantly upregulated SV2A protein levels were found in both NEPC cell lines and tumor tissues. PET imaging studies were carried out in NEPC xenograft models with 18F-SynVesT-1. Although 18F-SynVesT-1 is not a cancer imaging agent, it showed a significant uptake level in the SV2A+ tumor (NCI-H660: 0.70 ± 0.14 %ID/g at 50-60 min p.i.). The SV2A blockade resulted in a significant reduction of tumor uptake (0.25 ± 0.03 %ID/g, p = 0.025), indicating the desired SV2A imaging specificity. Moreover, the comparative PET imaging study showed that the DU145 tumors could be clearly visualized by 18F-SynVesT-1 but not 68Ga-PSMA-11 nor 68Ga-DOTATATE, further validating the role of SV2A-targeted imaging for noninvasive assessment of NED in PCa. In conclusion, we demonstrated that SV2A, highly expressed in NEPC, can serve as a promising target for noninvasive imaging evaluation of NED.

Long noncoding RNA WDFY3-AS2 suppresses tumor progression by acting as a competing endogenous RNA of microRNA-18a in ovarian cancer.

Ovarian cancer (OC) is a fatal cancer in women, mainly due to its aggressive nature and poor survival rate. The lncRNA-miRNA-mRNA (long noncoding RNA-microRNA-messenger RNA) interaction is promising biomarkers for the improving prognosis of OC. Therefore, we explored the regulatory mechanism of WDFY3-AS2/miR-18a/RORA axis involved in the biological activities of OC cells. Microarray analysis predicted differentially expressed lncRNA, miRNA, and mRNA related to OC, followed by investigating the relationship among them. The expression patterns of the identified lncRNA WDFY3-AS2, miR-18a, and RORA were measured in OC tissue and cells. Gain- and loss-of-function experiments were performed to characterize the effect of lncRNA WDFY3-AS2 on OC cells, as well as the involvement of miR-18a and RAR related orphan receptor A (RORA). The in vitro assays were validated by in vivo experiments. According to bioinformatics analysis, WDFY3-AS2 was speculated to affect OC by sponging miR-18a and modulating RORA. WDFY3-AS2 and RORA were underexpressed in OC, while miR-18a was highly expressed. Notably, WDFY3-AS2 acts as a competing endogenous RNA to sponge miR-18a and upregulate RORA. Upon overexpressing WDFY3-AS2 or inhibiting miR-18a, RORA expression was increased, thereby the OC cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) were suppressed, accompanied by enhanced apoptosis. In vivo experiments confirmed that the tumor growth was reduced in response to overexpressed WDFY3-AS2 or inhibited miR-18a. Taken together, the lncRNA WDFY3-AS2/miR-18a axis regulates the tumor progression of OC by targeting RORA, providing new insights for prevention and control of OC.

Interference with SMO increases chemotherapy drug sensitivity of A2780/DDP cells by inhibiting the Hh/Gli signaling pathway.

Aberrant activation of the Hedgehog (Hh)/Gli pathway contributes to the tumorigenesis of several human cancers, including ovarian cancers. We investigated the function of SMO on cell growth, drug resistance, and invasive ability in A2780/DDP cells. Moreover, we also tested the levels of the downstream target genes of the Hh/Gli pathway in SMO short hairpin RNA (shRNA) lentivirus-infected A2780/DDP cells. Western blot analysis results revealed that the Hh/Gli pathway was activated in cisplatin-resistant A2780/DDP cells. After infection by SMO shRNA lentivirus, the colony formation rate and invasive rate of cisplatin-resistant A2780/DDP cells were decreased. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that upon transfection with SMO shRNA, cell growth was decreased and drug sensitivity to cisplatin was upregulated. Moreover, interference with SMO decreased the expression of MMP-2, MMP-9, VEGF, and Snail in cisplatin-resistant cells. Thus, the Hh/Gli signaling pathway was aberrantly activated in A2780/DDP cells. The colony formation rate and invasive rate were decreased in SMO shRNA lentivirus-infected A2780/DDP cells. All results showed that inhibiting Hh/Gli signaling may negatively regulate the proliferation, invasion, and metastasis of cisplatin-resistant A2780/DDP cells, as well as increase the sensitivity of A2780/DDP to the chemotherapeutic drug of cisplatin.

Estrogen receptor coregulator binding modulator (ERX-11) enhances the activity of CDK4/6 inhibitors against estrogen receptor-positive breast cancers.

BACKGROUND: CDK4/6 inhibitors in combination with endocrine therapy (AE/AI/SERDs) are approved for the treatment of ER+ advanced breast cancer (BCa). However, not all patients benefit from CDK4/6 inhibitors therapy. We previously reported a novel therapeutic agent, ERX-11, that binds to the estrogen receptor (ER) and modulates ER-coregulator interactions. Here, we tested if the combination of ERX-11 with agents approved for ER+ BCa would be more potent. METHODS: We tested the effect of combination therapy using BCa cell line models, including those that have acquired resistance to tamoxifen, letrozole, or CDK4/6 inhibitors or have been engineered to express mutant forms of the ER. In vitro activity was tested using Cell Titer-Glo, MTT, and apoptosis assays. Mechanistic studies were conducted using western blot, reporter gene assays, RT-qPCR, and mass spectrometry approaches. Xenograft, patient-derived explants (PDEs), and xenograft-derived explants (XDE) were used for preclinical evaluation and toxicity. RESULTS: ERX-11 inhibited the proliferation of therapy-resistant BCa cells in a dose-dependent manner, including ribociclib resistance. The combination of ERX-11 and CDK4/6 inhibitor was synergistic in decreasing the proliferation of both endocrine therapy-sensitive and endocrine therapy-resistant BCa cells, in vitro, in xenograft models in vivo, xenograft-derived explants ex vivo, and in primary patient-derived explants ex vivo. Importantly, the combination caused xenograft tumor regression in vivo. Unbiased global mass spectrometry studies demonstrated profound decreases in proliferation markers with combination therapy and indicated global proteomic changes in E2F1, ER, and ER coregulators. Mechanistically, the combination of ERX-11 and CDK4/6 inhibitor decreased the interaction between ER and its coregulators, as evidenced by immunoprecipitation followed by mass spectrometry studies. Biochemical studies confirmed that the combination therapy significantly altered the expression of proteins involved in E2F1 and ER signaling, and this is primarily driven by a transcriptional shift, as noted in gene expression studies. CONCLUSIONS: Our results suggest that ERX-11 inhibited the proliferation of BCa cells resistant to both endocrine therapy and CDK4/6 inhibitors in a dose-dependent manner and that the combination of ERX-11 with a CDK4/6 inhibitor may represent a viable therapeutic approach.

Electrical Impedance Measurements of Biological Cells in Response to External Stimuli.

Dielectric spectroscopy (DS) is a noninvasive technique for real-time measurements of the impedance spectra of biological cells. DS enables characterization of cellular dielectric properties such as membrane capacitance and cytoplasmic conductivity. We have developed a lab-on-a-chip device that uses an electro-activated microwells array for capturing, DS measurements, and unloading of biological cells. Impedance measurements were conducted at 0.2 V in the 10 kHz to 40 MHz range with 6 s time resolution. An equivalent circuit model was developed to extract the cell membrane capacitance and cell cytoplasmic conductivity from the impedance spectra. A human prostate cancer cell line, PC-3, was used to evaluate the device performance. Suspension of PC-3 cells in low conductivity buffers (LCB) enhanced their dielectrophoretic trapping and impedance response. We report the time course of the variations in dielectric properties of PC-3 cells suspended in LCB and their response to sudden pH change from a pH of 7.3 to a pH of 5.8. Importantly, we demonstrated that our device enabled real-time measurements of dielectric properties of live cancer cells and allowed the assessment of the cellular response to variations in buffer conductivity and pH. These data support further development of this device toward single cell measurements.

Developing new targeting strategy for androgen receptor variants in castration resistant prostate cancer.

The presence of androgen receptor variant 7 (AR-V7) variants becomes a significant hallmark of castration-resistant prostate cancer (CRPC) relapsed from hormonal therapy and is associated with poor survival of CRPC patients because of lacking a ligand-binding domain. Currently, it still lacks an effective agent to target AR-V7 or AR-Vs in general. Here, we showed that a novel class of agents (thailanstatins, TSTs and spliceostatin A analogs) can significantly suppress the expression of AR-V7 mRNA and protein but in a less extent on the full-length AR expression. Mechanistically, TST-D is able to inhibit AR-V7 gene splicing by interfering the interaction between U2AF65 and SAP155 and preventing them from binding to polypyrimidine tract located between the branch point and the 3' splice site. In vivo, TST-D exhibits a potent tumor inhibitory effect on human CRPC xenografts leading to cell apoptosis. The machinery associated with AR gene splicing in CRPC is a potential target for drugs. Based on their potency in the suppression of AR-V7 responsible for the growth/survival of CRPC, TSTs representing a new class of anti-AR-V agents warrant further development into clinical application.

Identification of substituent groups and related genes involved in salecan biosynthesis in Agrobacterium sp. ZX09.

Salecan, a soluble ß-1,3-D-glucan produced by a salt-tolerant strain Agrobacterium sp. ZX09, has been the subject of considerable interest in recent years because of its multiple bioactivities and unusual rheological properties in solution. In this study, both succinyl and pyruvyl substituent groups on salecan were identified by an enzymatic hydrolysis following nuclear magnetic resonance (NMR), HPLC, and MS analysis. The putative succinyltransferase gene (sleA) and pyruvyltransferase gene (sleV) were determined and cloned. Disruption of the sleA gene resulted in the absence of succinyl substituent groups on salecan. This defect could be complemented by expressing the sleA cloned in a plasmid. Thus, the sleA and sleV genes located in a 19.6-kb gene cluster may be involved in salecan biosynthesis. Despite the lack of succinyl substituents, the molecular mass of salecan generated by the sleA mutant did not substantially differ from that generated by the wild-type strain. Loss of succinyl substituents on salecan changed its rheological characteristics, especially a decrease in intrinsic viscosity.

CDK4/6 inhibitors promote PARP1 degradation and act synergistically with PARP inhibitors in non-small cell lung cancer.

Despite the widespread deregulation of CDK4/6 activity in non-small cell lung cancer (NSCLC), the clinical trials with CDK4/6 inhibitors (CDK4/6is) as a monotherapy have shown poor antitumor activity. However, our preclinical studies have revealed a significant potential for CDK4/6is to collaborate by influencing DNA damage repair pathways during radiotherapy. Given the considerable upregulation of PARP1 expression in NSCLC, we analyzed the efficacy of combined PARP and CDK4/6 inhibition in NSCLC models. Our findings demonstrate that CDK4/6is synergize with PARP inhibitors (PARPis) to inhibit the clonogenic growth of RB-proficient NSCLC models. This synergy is associated with increased accumulation of DNA damage, interrupted cell-cycle checkpoints, and enhanced apoptotic cell death. We showed that CDK4/6is mechanically promote PARP1 protein degradation, leading to decreased availability of DNA repair factors involved in homologous recombination and suppression of DNA repair competency. Furthermore, we showed that PARP trapping is required for this synergy. We then confirmed that combining PARPi and CDK4/6i blocked the growth of NSCLC xenografts in vivo and patient-derived explant models ex vivo. These findings reveal a previously uncharacterized impact of CDK4/6i on PARP1 levels in RB-proficient NSCLC models and the requirement of PARP trapping to render synergy between CDK4/6i and PARPi. Our research suggests that combining CDK4/6i with PARPi could be a promising therapeutic strategy for patients with RB-proficient NSCLC, potentially opening up new and more effective avenues for treatment.

A 1T'-MoTe2/GaN van der Waals Schottky junction for self-powered UV imaging and optical communication.

Schottky-type self-powered UV photodetectors are promising for next-generation imaging systems. Nevertheless, conventional device fabrication using high-energy metal deposition brings unintentional interface defects, leading to deteriorated device performance and inhomogeneities. Emerging two-dimensional (2D) metallic materials offer an alternative pathway to overcoming such limitations because of their naturally passivated surfaces and the ease of combining with mature bulk semiconductors via van der Waals (vdW) integration. Here, we report the controllable preparation of MoTe2 in the pure 1T' phase and the fabrication of a high-performance 1T'-MoTe2/GaN vdW Schottky photodiode. With the reduced interface states and suppressed dark current as low as 20 pA at zero bias, the photodiode exhibits a remarkable UV-to-visible (R350/R400) rejection ratio of 1.6 × 104, a stable photoresponsivity of ∼50 mA W-1 and a detectivity of 3.5 × 1012 Jones under 360 nm illumination. The photocurrent ON/OFF ratio reaches ∼4.9 × 106 under 10.5 mW irradiation (360 nm). In particular, the 1T'-MoTe2/GaN Schottky diode shows excellent weak-light detection capability, which could detect a 3 nW 360 nm laser and the light emission from a lighter with a pronounced Ilight/Idark ratio of ∼2. Finally, the applications of the device in self-powered UV imaging and optical communication are demonstrated. These results reveal the great prospects of 2D/3D integration in multifunctional optoelectronics, which may inspire novel 2D-related devices and expand their applications in widespread fields.

Non-linear associations between cardiovascular metabolic indices and metabolic-associated fatty liver disease: A cross-sectional study in the US population (2017-2020).

The cardiometabolic index (CMI) is an emerging and effective indicator for predicting the presence of metabolic-associated fatty liver disease (MAFLD). This study aims to investigate the relationship between CMI and MAFLD using data from NHANES 2017-2020. In this cross-sectional study, a total of 3,749 subjects were included. The study conducted a thorough analysis of CMI with three multivariate logistic regression models, subgroup analyses, and restricted cubic splines (RCS) were utilized. Using multifactorial logistic regression as the primary method of analysis, we found that a higher CMI was also significantly associated with an increased risk of MAFLD (OR = 1.45, 95% CI (1.05-2.01)). This result was further visualized by the RCS curve: There was a non-linear positive correlation between CMI and MAFLD incidence (the turning point is CMI = 0.4554). These findings were strongly reinforced by subsequent subgroup and sensitivity analyses. There is a robust positive relationship between the CMI and the risk of MAFLD, providing valuable clinical benefits for early detection and screening of MAFLD. It is important to highlight the presence of a non-linear association between CMI and MAFLD, with an inflection point identified at CMI = 0.4554.

Therapeutic effects of chamomile volatile oil nanoemulsion/Bletilla striata polysaccharides gels on atopic dermatitis.

Atopic dermatitis (AD) is a prevalent chronic skin condition characterized by complex immune responses. Chamomile possesses potent anti-inflammatory properties and has been widely used in treating various skin diseases. This study aimed to assess the therapeutic benefits of chamomile volatile oil nanoemulsion gels (CVO-NEGs) for the treatment of AD. Chamomile volatile oil nanoemulsions (CVO-NEs) were prepared using the phase transition method, yielding spherical nanoparticles with a particle size of 19.07 nm. Subsequently, Bletilla striata polysaccharides were employed to encapsulate CVO-NEs, resulting in the formation of CVO-NEGs. In vivo studies demonstrated that the preparation of CVO-NEGs enhanced the biological activity of volatile oil in AD therapy. Histopathological results indicated that CVO-NEGs reduced skin damage, epidermal thickness, and mast cell infiltration. CVO-NEGs suppressed IgG production and reduced the levels of cytokines, including TNF-α, IL-4, and IFN-γ, in AD mice. Furthermore, flow cytometry revealed that CVO-NEGs were involved in regulating the differentiation of CD4+ T cell subsets. The immune imbalance of Th1/Th2 in AD mice can be controlled, resulting in a reduction in the hypersensitivity reaction caused by excessive Th2 activation. In conclusion, the present study confirms that CVO-NEGs have the potential to serve as an effective alternative treatment for AD.

Knockdown of Programmed Death 1 Inhibited Progression of Papillary Thyroid Carcinoma in Mice.

BACKGROUND: PD-L1 and PD1 mainly focused on melanoma, lung cancer and other tumors, while the related studies on early lymph node metastasis of papillary thyroid carcinoma were rarely reported. OBJECTIVE: For elucidating the role of programmed death 1 (PD1)/programmed death ligand 1 (PD-L1) pathway in tumor growth of papillary thyroid carcinoma (PTC). METHODS: Human thyroid cancer cell line and human normal thyroid cell line were obtained and transfected with si-PD1 or pCMV3-PD1 for the construction of PD1 knockdown or overexpression models. BALB/c mice were purchased for in vivo studies. Nivolumab was implemented for in vivo inhibition of PD1. Western blotting was performed for determining protein expression, while RTqPCR was used to measure relative mRNA levels. RESULTS: The PD1 and PD-L1 levels were both significantly upregulated in PTC mice, while the knockdown of PD1 downregulated both PD1 and PD-L1 levels. Protein expression of VEGF and FGF2 was increased in PTC mice, while si-PD1 decreased their expression. Silencing of PD1 using si-PD1 and nivolumab both inhibited tumor growth in PTC mice. CONCLUSION: Suppressing PD1/PD-L1 pathway significantly contributed to the tumor regression of PTC in mice.

Care intervention on psychological outcomes among patients admitted to intensive care unit: an umbrella review of systematic reviews and meta-analyses.

BACKGROUND: Numerous studies have explored care interventions to improve the psychological outcome of intensive care unit (ICU) patients, but inconclusive evidence makes it difficult for decision-makers, managers, and clinicians to get familiar with all available literature and find appropriate interventions. This umbrella review aimed to analyze the relationship between care intervention and psychological outcomes of ICU patients based on existing systematic reviews. METHODS: An umbrella review of evidence across systematic reviews and meta-analyses published between 1987 and 2023 was undertaken. We systematically searched reviews that examined the association between care intervention and the improvement of adverse psychological outcomes in ICU patients using PubMed, EMBASE, Web of Science, Cochrane Library, and manual reference screening. The measurement tool (AMSTAR 2) was applied to evaluate the methodological quality of included studies. The excess significance bias, between-study heterogeneity expressed by I2, small-study effect, and evidence class were estimated. RESULTS: A total of 5110 articles were initially identified from the search databases and nine of them were included in the analysis. By applying standardized criteria, only weak evidence was observed in 13 associations, even though most included reviews were of moderate to high methodological quality. These associations pertained to eight interventions (music therapy, early rehabilitation, post-ICU follow-up, ICU diary, information intervention, preoperative education, communication and psychological support, surrogate decision-making) and five psychological outcomes (post-intensive care syndrome, transfer anxiety, post-traumatic stress disorder, anxiety, and depression). Weak or null association was shown among the rest of the associations (e.g., weak association between music therapy and maternal anxiety or stress level). CONCLUSIONS: The evidence of these eight supporting interventions to improve the adverse psychological outcomes of ICU patients and caregivers was weak. Data from more and better-designed studies with larger sample sizes are needed to establish robust evidence.

Riluzole Suppresses Growth and Enhances Response to Endocrine Therapy in ER+ Breast Cancer.

Background: Resistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer remains a significant clinical problem. Riluzole is FDA-approved for the treatment of amyotrophic lateral sclerosis. A benzothiazole-based glutamate release inhibitor with several context-dependent mechanism(s) of action, riluzole has shown antitumor activity in multiple malignancies, including melanoma, glioblastoma, and breast cancer. We previously reported that the acquisition of tamoxifen resistance in a cellular model of invasive lobular breast cancer is accompanied by the upregulation of GRM mRNA expression and growth inhibition by riluzole. Methods: We tested the ability of riluzole to reduce cell growth, alone and in combination with endocrine therapy, in a diverse set of ER+ invasive ductal and lobular breast cancer-derived cell lines, primary breast tumor explant cultures, and the estrogen-independent, ESR1-mutated invasive lobular breast cancer patient-derived xenograft model HCI-013EI. Results: Single-agent riluzole suppressed the growth of ER+ invasive ductal and lobular breast cancer cell lines in vitro, inducing a histologic subtype-associated cell cycle arrest (G0-G1 for ductal, G2-M for lobular). Riluzole induced apoptosis and ferroptosis and reduced phosphorylation of multiple prosurvival signaling molecules, including Akt/mTOR, CREB, and Fak/Src family kinases. Riluzole, in combination with either fulvestrant or 4-hydroxytamoxifen, additively suppressed ER+ breast cancer cell growth in vitro. Single-agent riluzole significantly inhibited HCI-013EI patient-derived xenograft growth in vivo, and the combination of riluzole plus fulvestrant significantly reduced proliferation in ex vivo primary breast tumor explant cultures. Conclusion: Riluzole may offer therapeutic benefits in diverse ER+ breast cancers, including lobular breast cancer.

Susceptibility of Hep3B cells in different phases of cell cycle to tBid.

tBid is a pro-apoptotic molecule. Apoptosis inducers usually act in a cell cycle-specific fashion. The aim of this study was to elucidate whether effect of tBid on hepatocellular carcinoma (HCC) Hep3B cells was cell cycle phase specific. We synchronized Hep3B cells at G0/G1, S or G2/M phases by chemicals or flow sorting and tested the susceptibility of the cells to recombinant tBid. Cell viability was measured by MTT assay and apoptosis by TUNEL. The results revealed that tBid primarily targeted the cells at G0/G1 phase of cell cycle, and it also increased the cells at the G2/M phase. 5-Fluorouracil (5-FU), on the other hand, arrested Hep3B cells at the G0/G1 phase, but significantly reduced cells at G2/M phase. The levels of cell cycle-related proteins and caspases were altered in line with the change in the cell cycle. The combination of tBid with 5-FU caused more cells to be apoptotic than either agent alone. Therefore, the complementary effect of tBid and 5-FU on different phases of the cell cycle may explain their synergistric effect on Hep3B cells. The elucidation of the phase-specific effect of tBid points to a possible therapeutic option that combines different phase specific agents to overcome resistance of HCC.

Thickness dependence of ferroelectricity in Langmuir-Blodgett multilayer films of hemicyanine dyes.

The thickness dependence of ferroelectricity in hemicyanine Langmuir-Boldgett multilayer films was reported in this paper. By the observed ferroelectric hysteresis loop, it was found that the coercive field decreased with increasing of film thickness monotonously and may be approximated by a power law Ec infinity N(-4/3) in the range from 30 to 200 nm, which is consistent with other conventional ferroelectric materials. The measurement of dielectric properties give the optimum thickness about 60 nm of hemicyanine LB films and their optimum value as ferroelectric storage-devices has the same order of magnitude as copolymer's P(VDF-TrFE) (70:30 mol%).