Thousands of conductance levels in memristors integrated on CMOS.

Neural networks based on memristive devices1-3 have the ability to improve throughput and energy efficiency for machine learning4,5 and artificial intelligence6, especially in edge applications7-21. Because training a neural network model from scratch is costly in terms of hardware resources, time and energy, it is impractical to do it individually on billions of memristive neural networks distributed at the edge. A practical approach would be to download the synaptic weights obtained from the cloud training and program them directly into memristors for the commercialization of edge applications. Some post-tuning in memristor conductance could be done afterwards or during applications to adapt to specific situations. Therefore, in neural network applications, memristors require high-precision programmability to guarantee uniform and accurate performance across a large number of memristive networks22-28. This requires many distinguishable conductance levels on each memristive device, not only laboratory-made devices but also devices fabricated in factories. Analog memristors with many conductance states also benefit other applications, such as neural network training, scientific computing and even 'mortal computing'25,29,30. Here we report 2,048 conductance levels achieved with memristors in fully integrated chips with 256 × 256 memristor arrays monolithically integrated on complementary metal-oxide-semiconductor (CMOS) circuits in a commercial foundry. We have identified the underlying physics that previously limited the number of conductance levels that could be achieved in memristors and developed electrical operation protocols to avoid such limitations. These results provide insights into the fundamental understanding of the microscopic picture of memristive switching as well as approaches to enable high-precision memristors for various applications. Fig. 1 HIGH-PRECISION MEMRISTOR FOR NEUROMORPHIC COMPUTING.: a, Proposed scheme of the large-scale application of memristive neural networks for edge computing. Neural network training is performed in the cloud. The obtained weights are downloaded and accurately programmed into a massive number of memristor arrays distributed at the edge, which imposes high-precision requirements on memristive devices. b, An eight-inch wafer with memristors fabricated by a commercial semiconductor manufacturer. c, High-resolution transmission electron microscopy image of the cross-section view of a memristor. Pt and Ta serve as the bottom electrode (BE) and top electrode (TE), respectively. Scale bars, 1 µm and 100 nm (inset). d, Magnification of the memristor material stack. Scale bar, 5 nm. e, As-programmed (blue) and after-denoising (red) currents of a memristor are read by a constant voltage (0.2 V). The denoising process eliminated the large-amplitude RTN observed in the as-programmed state (see Methods). f, Magnification of three nearest-neighbour states after denoising. The current of each state was read by a constant voltage (0.2 V). No large-amplitude RTN was observed, and all of the states can be clearly distinguished. g, An individual memristor on the chip was tuned into 2,048 resistance levels by high-resolution off-chip driving circuitry, and each resistance level was read by a d.c. voltage sweeping from 0 to 0.2 V. The target resistance was set from 50 µS to 4,144 µS with a 2-µS interval between neighbouring levels. All readings at 0.2 V are less than 1 µS from the target conductance. Bottom inset, magnification of the resistance levels. Top inset, experimental results of an entire 256 × 256 array programmed by its 6-bit on-chip circuitry into 64 32 × 32 blocks, and each block is programmed into one of the 64 conductance levels. Each of the 256 × 256 memristors has been previously switched over one million cycles, demonstrating the high endurance and robustness of the devices.

SMAD4 regulates the progression of cholangiocarcinoma by modulating the expression of STING1.

SMAD4 is a tumour suppressor and an important regulator of tumour immune scape which is downregulated in cholangiocarcinoma (CCA). STING1 is a vital sensing factor of abnormal DNA; however, the correlation between SMAD4 and STING1 and the role of the SMAD4-STING1 interaction in the progression of CCA have not yet been evaluated. Public database was analysed to reveal the expression of SMAD4 and STING1. A cohort comprising 50 iCCA, 113 pCCA and 119 dCCA patients was assembled for the study. Immunohistochemistry was employed to evaluate the expression levels of STING1 and SMAD4. In vitro transwell and CCK8 assays, along with luciferase reporter assay, were conducted to analyse the potential regulatory mechanisms of SMAD4 on the expression of STING1. Expression of SMAD4 and STING1 were downregulated in CCA tumours and STING1 expression correlated with SMAD4 expression. The overexpression of SMAD4 was found to suppress the migration, invasion and proliferation capabilities of CCA cells; whereas, the knockdown of SMAD4 enhanced these abilities. Furthermore, it was observed that SMAD4 translocated into the nucleus following TGF-ß1 stimulation. Knockdown of SMAD4 resulted in the inhibition of STING1 transcriptional activity, whereas the overexpression of SMAD4 promoted the transcriptional activity of STING1. Clinically, low STING1 and SMAD4 expression indicated poor prognosis in CCA, and simultaneously low expression of STING1 and SMAD4 predicts poorer patient survival. SMAD4 regulates the expression of STING1 through its transcription regulating function. Dual low expression of STING1 and SMAD4 had more power in predicting patient survival. These results indicate that SMAD4-silenced CCA may downregulate its STING1 expression to adapt to the immune system.

Hepatectomy After Conversion Therapy Using Tyrosine Kinase Inhibitors Plus Anti-PD-1 Antibody Therapy for Patients with Unresectable Hepatocellular Carcinoma.

BACKGROUND: Combined treatment with tyrosine kinase inhibitors (TKI) plus anti-PD-1 antibodies showed high anti-tumor efficacy and made conversion resection possible for patients with unresectable hepatocellular carcinoma (HCC). However, long-term survival has not been reported. METHODS: A cohort of consecutive patients who received combined TKI/anti-PD-1 antibodies as first-line treatment for initially unresectable HCC at the authors' hospital between August 2018 and September 2020 was eligible for this study. Patients who were responding to systemic therapy and met the criteria for hepatectomy underwent liver resection with curative intention. The study also investigated the association of clinical factors with successful conversion resection and postoperative recurrence. RESULTS: The study enrolled 101 patients including 24 patients (23.8 %) who underwent R0 resection a median of 3.9 months (interquartile range: 2.5-5.9 months) after initiation of systemic therapy. Patients with an Eastern cooperative oncology group performance status of 0, fewer intrahepatic tumors, or a radiographic response to systemic therapy were more likely to be able to receive curative resection. After a median follow-up period of 21.5 months, hepatectomy was independently associated with a favorable overall survival (hazard ratio [HR], 0.050; 95 % confidence interval [CI], 0.007-0.365; P = 0.003). For the 24 patients who underwent surgery, the 12-month recurrence-free survival and overall survival rates were respectively 75% and 95.8%. Achieving a pathologic complete response (n = 10) to systemic therapy was associated with a favorable recurrence-free survival after resection, with a trend toward significance (HR, 0.345; 95% CI, 0.067-1.785; P = 0.187). CONCLUSIONS: Selected patients with initially unresectable HCC can undergo hepatectomy after systemic therapy with combined TKI/anti-PD-1 antibodies. In this study, conversion resection was associated with a favorable prognosis.

Radiographic and α-fetoprotein response predict pathologic complete response to immunotherapy plus a TKI in hepatocellular carcinoma: a multicenter study.

BACKGROUND: Pathologic complete response (pCR) following preoperative systemic therapy is associated with improved outcomes after subsequent liver transplant/resection in hepatocellular carcinoma (HCC). However, the relationship between radiographic and histopathological response remains unclear. METHODS: We retrospectively examined patients with initially unresectable HCC who received tyrosine kinase inhibitor (TKI) plus anti-programmed death 1 (PD-1) therapy before undergoing liver resection between March 2019 and September 2021 across 7 hospitals in China. Radiographic response was evaluated using mRECIST. A pCR was defined as no viable tumor cells in resected samples. RESULTS: We included 35 eligible patients, of whom 15 (42.9%) achieved pCR after systemic therapy. After a median follow-up of 13.2 months, tumors recurred in 8 non-pCR and 1 pCR patient. Before resection, there were 6 complete responses, 24 partial responses, 4 stable disease cases, and 1 progressive disease case, per mRECIST. Predicting pCR by radiographic response yielded an area under the receiver operating characteristic curve (AUC) of 0.727 (95% CI: 0.558-0.902), with an optimal cutoff value of 80% reduction in the enhanced area in MRI (called major radiographic response), which had a 66.7% sensitivity, 85.0% specificity, and a 77.1% diagnostic accuracy. When radiographic response was combined with α-fetoprotein response, the AUC was 0.926 (95% CI: 0.785-0.999); the optimal cutoff value was 0.446, which had a 91.7% sensitivity, 84.6%, specificity, and an 88.0% diagnostic accuracy. CONCLUSIONS: In patients with unresectable HCC receiving combined TKI/anti-PD 1 therapy, major radiographic response alone or combined with α-fetoprotein response may predict pCR.

The accuracy of screening instruments for sarcopenia: a diagnostic systematic review and meta-analysis.

OBJECTIVE: This review aimed to summarise the diagnostic accuracy of screening tools for sarcopenia. METHODS: We conducted a systematic review along with a critical appraisal of published studies on screening tools for sarcopenia. We assessed the measurement properties of screening instruments using the consensus-based standards for selecting health measurement instruments (COSMIN) checklist. We evaluated the risk bias of the included studies using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. The diagnostic test accuracy of instruments for sarcopenia was reported using sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR). RESULTS: We screened 7,120 titles and abstracts; 42 studies including five screening tools for sarcopenia were included. The overall study quality assessed by the QUADAS-2 tool was moderate to good. Of the five screening tools, three instruments had specificities ≥85%: 92% [95% confidence interval (CI): 63-99%] for the SARC-F modified version, 87% (95% CI: 82-90%) for the SARC-F and 85% (95% CI: 77-90%) for the Ishii score. Three tools had sensitivity ≥75%, namely, MSRA 82% (95% CI: 69-90%), Ishii score 79% (95% CI: 62-89%) and U-TEST 76%. PLR higher than 5.0 were present for the Ishii score and SARC-F modified versions; the Ishii score also had the best NLR of 0.25 of all scales. CONCLUSION: The MSRA and Ishii score had excellent sensitivity for sarcopenia screening at an early stage; SARC-F modified versions and Ishii score had superior specificity for sarcopenia diagnosis.

Is waist-calf circumference ratio associated with frailty in older adults? Findings from a cohort study.

BACKGROUND: The waist-calf circumference ratio (WCR) has been suggested as a potential indicator of visceral adiposity. Nevertheless, the relationship between WCR and the risk of frailty remains unclear. Therefore, our study aimed to investigate the association between WCR and longitudinal changes in WCR with frailty risk in older adults. METHODS: We included 2359 participants aged ≥ 65 years without frailty (frailty index [FI] ≤ 0.21) from the Chinese Longitudinal Healthy Longevity Survey in the 2014 wave. The follow-up was conducted in 2018. We investigated the relationship of WCR, waist circumference (WC), and calf circumference (CC) with frailty using both the Cox proportional hazards model and the generalized estimating equation (GEE). RESULTS: During a median follow-up of 4.0 years, 668 (28.2%) frailty occurred. Those with higher WCR and WC had a significantly increased risk of frailty (fifth quintile compared with first quintile: hazard ratio [HR] = 1.59, 95% confidence interval [CI] 1.24-2.04 for WCR; HR = 1.69, 95% CI 1.27-2.24 for WC), whereas those in the fourth quintile of CC had a lower likelihood of developing frailty compared to those in the first quintile (HR = 0.67, 95% CI 0.50-0.89). Interaction analyses showed that the effects of WCR on frailty were more pronounced in females (P-interaction = 0.016). GEE analyses revealed that increased WCR and WC were associated with a higher risk of frailty (odds ratio [OR] = 1.74, 95% CI 1.43-2.12 for WCR; OR = 1.03, 95% CI 1.02-1.04 for WC), while CC showed opposite results (OR = 0.95, 95% CI 0.93-0.97). CONCLUSIONS: A higher WCR and WC, as well as a lower CC, were significantly associated with higher frailty. Of these measures, WCR demonstrated the strongest association with frailty, suggesting that having a combination of high central fat and low lean body mass may increase the risk of developing frailty.

[Forkhead Box M1 Regulates the Proliferation,Invasion,and Drug Resistance of Gastric Cancer Cells via circ_NOTCH1].

Objective To investigate the impacts of forkhead box M1(FOXM1)on the proliferation,invasion,and drug resistance of gastric cancer cells by regulating the circular RNA circ_NOTCH1.Methods Western blotting and real-time quantitative PCR were performed to determine the expression of FOXM1 protein and circ_NOTCH1,respectively,in the gastric cancer tissue,para-carcinoma tissue,human normal gastric mucosa epithelial cell line GES-1 and gastric cancer cell lines MGC-803,HGC-27,and BGC-823.BGC-823 cells were classified into the following groups:control,short hairpin RNA FOXM1(sh-FOXM1)and negative control(sh-NC),small interfering RNA circ_NOTCH1(si-circ_NOTCH1)and negative control(si-NC),and sh-FOXM1+circ_NOTCH1 overexpression plasmid(sh-FOXM1+pcDNA-circ_NOTCH1)and sh-FOXM1+negative control(sh-FOXM1+pcDNA).CCK-8 assay and clone formation assay were employed to measure the cell proliferation,and Transwell assay to measure cell invasion.After treatment with 1.0 mg/L adriamycin for 48 h,the cell resistance in each group was analyzed.Western blotting was employed to determine the expression levels of FOXM1,proliferating cell nuclear antigen(PCNA),Bax,multi-drug resistance-associated protein 1(MRP1),and multi-drug resistance gene 1(MDR1).RNA pull-down and RNA immunoprecipitation were employed to examine the binding of circ_NOTCH1 to FOXM1 protein.Results Compared with those in the para-carcinoma tissue,the expression levels of FOXM1 protein and circ_NOTCH1 in the gastric cancer tissue were up-regulated(all P<0.001).Compared with GES-1 cells,MGC-803,HGC-27,and BGC-823 cells showed up-regulated expression levels of FOXM1 protein and circ_NOTCH1(all P<0.001).Compared with the control group and sh-NC group,the sh-FOXM1 group with down-regulated expression of FOXM1 protein and circ_NOTCH1 showed decreased optical density value,clone formation rate,cell invasion number,and cell viability,down-regulated expression of PCNA,MRP1,and MDR1,and up-regulated expression of Bax protein in BGC-823 cells(all P<0.001).Compared with the control group and the si-NC group,the si-circ_NOTCH1 group with down-regulated expression of circ_NOTCH1 showed decreased optical density value,clone formation rate,cell invasion number,and cell viability,down-regulated expression of PCNA,MRP1,and MDR1,and up-regulated expression of Bax protein in BGC-823 cells(all P<0.001).Compared with sh-FOXM1 group and sh-FOXM1+pcDNA group,the sh-FOXM1+pcDNA-circ_NOTCH1 group with up-regulated expression of circ_NOTCH1 showed increased optical density value,clone formation rate,cell invasion number,and cell viability,up-regulated expression of PCNA,MRP1,and MDR1,and down-regulated expression of Bax protein(all P<0.001).FOXM1 protein was able to interact with circ_NOTCH1.Conclusion Interference with FOXM1 may inhibit the proliferation,invasion,and drug resistance of gastric cancer cells by silencing circ_NOTCH1 expression.

The prevalence and associated factors of motoric cognitive risk syndrome in multiple ethnic middle-aged to older adults in west China: a cross-sectional study.

BACKGROUND AND PURPOSE: Motoric cognitive risk (MCR) syndrome characterized by subjective cognitive complaints and slow gait has been proposed and validated as a pre-dementia syndrome. The overall and specific ethnic prevalence of MCR and the associated factors are poorly understood in middle-aged to older community-dwelling residents in west China. METHODS: The present study included 6091 samples from the prospective cohort study, West China Health and Aging Trend (WCHAT). Multidimensional factors of demography, lifestyle, social support, anthropometrics and body components, and clinical status were investigated and analyzed by univariate and multivariate logistic regression models. Lasso regression and K-fold cross-validation were conducted to construct the most predictive model with fitted factors. RESULTS: The overall prevalence of MCR was 9.74%, and ethnically the prevalence was 14.25% in Tibetan, 11.03% in Yi, 10.72% in Han, 5.18% in Uighur and 4.55% in Qiang, respectively. In the adjusted models, the positively associated risk factors included diabetes mellitus (odds ratio [OR] = 1.51, p = 0.007), osteoarthritis (OR = 1.50, p = 0.002), depression (OR = 1.36, p = 0.005), poor sleep (OR = 1.21, p = 0.045), comorbidity (OR = 1.49, p = 0.001) and falls in the last 12 months (OR = 1.34, p = 0.031). Of note, every 1-unit increase of value in stroke was associated with an approximate 3-fold higher risk of having MCR, whilst in high-density lipoprotein with a 30% lower risk of MCR,respectively. CONCLUSIONS: Profiles of MCR from the aspects of ethnicity and the presenium stage need further exploration. It is a promising strategy to apply MCR as a primary prevention tool to prevent dementia.

A novel semiautomatic Chinese keywords instrument screening delirium based on electronic medical records.

BACKGROUND: Delirium is frequently unrecognized due to the absence of regular screening. In addition to validated bedside tools, the computer-assisted instrument based on clinical notes from electronic medical records may be useful. AIMS: To assess the psychometric properties of a Chinese-chart-based keyword instrument for semiautomatically screening delirium using Natural language processing (NLP) based on clinical notes from electronic medical records. METHODS: The patients were admitted to West China Hospital from January 2015 to December 2017. Grouping patients based on the medical notes, those with accessible physician documents but no nurse documents were classified as the physician & no-nurse (PNN) group, while those with accessible physician and nurse documents were classified as the physician & nurse (PN) group. The psychometric properties, test-retest reliability, internal consistency reliability (Cronbach's α), and criterion validity were calculated. Using receiver operating characteristic (ROC) analysis, the criterion validity of delirium was evaluated in comparison to the results of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. RESULTS: A total of 779 patients were enrolled in the study. Their ages ranged from 65 to 103 years (82.5 ± 6.5), with men accounting for 71.9% of the total. A total of 312 patients had access to only physician documents in the physician & no-nurse (PNN) group, whereas 467 patients had access to both physician and nurse documents in the physician & nurse (PN) group. All 779 patients had a Cronbach's alpha of 0.728 in terms of reliability, with 100% test-retest reliability. The area under the ROC curve (AUC) values of the delirium screening instrument for criterion validity were 0.76 (all patients, n = 779), 0.72 (PNN, n = 312), and 0.79 (PN, n = 467), respectively. CONCLUSION: A delirium screening instrument composed of Chinese keywords that can be easily and quickly obtained from electronic medical records was developed, which improved delirium detection in older people. TRIAL REGISTRATION: Not applicable.

Reliability and validity of two hand dynamometers when used by community-dwelling adults aged over 50 years.

BACKGROUND: The Jamar hydraulic dynamometer is a widely recognized tool for measuring grip strength. Nevertheless, the devices used most often in Asian countries are spring-type dynamometers, represented by the CAMRY dynamometer or Smedley dynamometer. We aimed to evaluate the reliability and validity of the CAMRY dynamometer compared with the Jamar dynamometer. METHODS: This was a cross-sectional study using a random crossover design in the grip strength test with two dynamometers. A total of 1064 healthy community-dwelling older adults aged 50-90 years old, which included 686 minorities and 378 Han Chinese, were recruited into the study from July to September 2021. We assessed the reliability and validity of the CAMRY EH101 dynamometer, and the Jamar dynamometer was regarded as the reference device. The order of testing with two dynamometers was randomized in a 1:1 ratio, with a 10-min gap between the two devices. Intraclass correlation coefficients (ICCs) and Bland-Altman analysis were calculated to assess reliability and validity between the two devices. RESULTS: The average handgrip strength (HGS) values at six times by the Jamar and CAMRY devices were 25.0 ± 7.9 kg and 24.6 ± 7.5 kg, respectively. The ICC values between the two devices were 0.815-0.854, and the systematic bias underestimated by the CAMRY dynamometer was 0.5 kg in men and 0.6 kg in women. We carried out a linear regression equation by sex, and their relationship was found as follows: male HGS (kg)Jamar = 8.001 + 0.765 × HGS (kg)CAMRY; female HGS (kg)Jamar = 3.681 + 0.840 × HGS (kg)CAMRY. CONCLUSIONS: The CAMRY EH101 dynamometer provides excellent reliability and validity. This device can serve as a reliable, inexpensive, and practical device to assess grip strength in geriatric clinical practice. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2100046367 ; Date of clinical trial reistration: 15/05/2021.

Barriers to prescribing oral anticoagulants to inpatients aged 80 years and older with nonvalvular atrial fibrillation: a cross-sectional study.

BACKGROUND: To investigate the temporal trend of the prevalence of underprescription of anticoagulation treatment and explore the factors associated with underprescription of oral anticoagulants (OACs) among inpatients aged ≥ 80 years with nonvalvular atrial fibrillation (NVAF). METHODS: We retrospectively reviewed the medical records of inpatients with a discharge diagnosis of NVAF from a medical database. We used the Pearson chi-square or Fisher's exact test to compare categorical variables between patients with and without OAC prescriptions during hospitalization. Logistic regression analysis was used to assess the association between risk factors and underprescription of OACs. RESULTS: A total of 4375 patients aged ≥ 80 years with AF were assessed in the largest academic hospital in China from August 1, 2016, to July 31, 2020, and 3165 NVAF patients were included. The prevalence of underprescription of OACs was 79.1% in 2017, 71.3% in 2018, 64.4% in 2019, and 56.1% in 2020. Of all participants, 2138 (67.6%) were not prescribed OACs; 66.3% and 68.2% of patients with and without prior stroke did not receive OACs, respectively. Age (85-89 vs 80-84, OR = 1.48, 95% CI (1.25-1.74); 90 + vs 80-84, OR = 2.66, 95% CI: 2.09-3.42), clinical department where patients were discharged (Reference = Cardiology, Geriatrics: OR = 2.97, 95% CI: 2.45- 3.61; neurology: OR = 1.25, 95% CI: 0.96, 1.63; others: OR = 4.23, 95% CI: 3.43- 5.24), use of antiplatelets (OR = 1.69, 95% CI: 1.45- 1.97), and history of stroke (OR = 0.83, 95% CI: 0.71- 0.98 adjusted age), and dementia (OR = 2.16, 95% CI: 1.60- 2.96) were significantly associated with not prescribing OACs. CONCLUSIONS: The prevalence of underprescription of OACs has decreased over the past several years. The rate of underprescription of OACs was higher among NVAF patients who were older, prescribed antiplatelets, discharged from nondepartmental cardiology, and suffered from comorbidities. This study found iatrogenic factors affecting the underprescription of OACs in inpatients aged ≥ 80 years, providing clues and a basis for the standardized use of OACs in inpatients.

Hsa_circ_0007142 contributes to cisplatin resistance in esophageal squamous cell carcinoma via miR-494-3p/LASP1 axis.

BACKGROUND: Chemoresistance is one of the major obstacles for tumor treatment. Circular RNAs (circRNAs) have been confirmed to play vital roles in chemoresistance of cancer, including esophageal squamous cell carcinoma (ESCC). We investigated the roles and mechanisms of circ_0007142 in cisplatin (DDP) resistance of ESCC. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the levels of circ_0007142, DOCK1 mRNA, microRNA-494-3p (miR-494-3p) and LIM And SH3 Protein 1 (LASP1) mRNA. RNase R assay was conducted to analyze the characteristic of circ_0007142. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate IC50 of DDP. Flow cytometry analysis, 5-ethynyl-2'-deoxyuridine (EdU) assay and transwell assay were carried out to examine cell apoptosis, proliferation and invasion, respectively. Dual-luciferase reporter assay was employed to verify the association between miR-494-3p and circ_0007142 or LASP1. Murine xenograft assay was conducted to investigate the role of circ_0007142 in DDP resistant in vivo. The protein level of LASP1 in tumors was measured by Immunohistochemistry (IHC) analysis. RESULTS: Circ_0007142 was upregulated in DDP-resistant ESCC tissues and cells. Circ_0007142 knockdown improved DDP sensitivity, induced cell apoptosis and hampered cell proliferation and invasion in DDP-resistant ESCC cells. Circ_0007142 functioned as the sponge for miR-494-3p and miR-494-3p inhibition reversed the impacts of circ_0007142 knockdown on DDP resistance, cell apoptosis, proliferation, and invasion. LASP1 was a target of miR-494-3p, and the effects on DDP resistance, cell apoptosis, growth, and invasion mediated by LASP1 downregulation were rescued by miR-494-3p inhibition. Moreover, circ_0007142 knockdown enhanced DDP sensitivity in vivo. CONCLUSION: Circ_0007142 improved DDP resistance of ESCC by upregulating LASP1 via sponging miR-494-3p.

Magnetic Anisotropy: Structural Correlation of a Series of Chromium(II)-Amidinate Complexes.

Systematic substituent variations on amidinate ligands bring delicate changes of CrN4 coordination in a family of chromium(II) complexes with the common formula of Cr(RNC(CH3)NR)2, where R = iPr (1), Cy (2), Dipp (Dipp = 2, 6-diisopropylphenyl) (3), and tBu (4). With the largest substituent group, 4 shows the largest distortion of the N4 coordination geometry from square-planar to seesaw shape, which leads to its field-induced single-molecule magnet (SMM) behavior. This is an indication that 4 has the strongest axial magnetic anisotropy and/or optimized magnetic relaxation process. Combined with high-frequency/field electron paramagnetic resonance (HF-EPR) experiments and ab initio calculations, we deduce that the smallest energy gap between ground 4Ψ0 and the first excited 4Ψ1 orbitals in 4 contributes the most to its strongest magnetic anisotropy. Moreover, the lower E value of 4 ensures its being a field-induced SMM. Specifically, the D and E values were found to be correlated to the dihedral angle between the ΔN1CrN2 and ΔN3CrN4 triangles, indicating that distortion from ideal square-planar geometry to the seesaw help increase axial magnetic anisotropy and suppress the transversal part. Thus, the study on this system not only expands the family of Cr(II)-based SMMs but also contributes to a deeper understanding of magneto-structural correlation in four-coordinate Cr(II) SMMs.

Albumin-to-alkaline phosphatase ratio as a predictor of tumor recurrence and prognosis in patients with early-stage hepatocellular carcinoma undergoing radiofrequency ablation as initial therapy.

OBJECTIVE: Albumin-to-alkaline phosphatase ratio (AAPR), a newly developed blood biomarker, has been reported to have prognostic value in several types of cancer. This study aimed to investigate the predictive value of AAPR in patients with early-stage hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA) as initial therapy. METHODS: This retrospective study analyzed 445 patients with newly diagnosed HCC undergoing RFA as initial therapy. A series of survival analyses were performed to evaluate the prognostic value of AAPR. Univariate and multivariate analyses were performed to identify independent prognostic factors. An AAPR-based nomogram was constructed, and its predictive performance was validated. RESULTS: Patients with a low AAPR had a significantly reduced recurrence-free survival (RFS) and overall survival (OS) compared with those with a high AAPR. AAPR was found to be an independent prognostic indicator and showed superior discrimination efficacy than other liver function indices. The AAPR-based nomogram had a concordance index value of 0.72 (95% confidence interval [CI]: 0.65-0.79) in the training cohort and 0.72 (95% CI: 0.63-0.81) in the validation cohort, which significantly outperformed other existing staging systems. CONCLUSIONS: AAPR serves as a promising indicator of prognosis in patients with early-stage HCC undergoing RFA. The AAPR-based nomogram might contribute to individualized prognosis prediction and clinical decision making.

[Research of relationship between frailty and gut microbiota on middle-aged and the aged patients with diabetes].

Gut microbiota plays an important role in development of diabetes with frailty. Therefore, it is of great significance to study the structural and functional characteristics of gut microbiota in Chinese with frailty. Totally 30 middle-aged and the aged participants in communities with diabetes were enrolled in this study, and their feces were collected. At the same time, we developed a metagenome analysis to explore the different of the structural and functional characteristics between diabetes with frailty and diabetes without frailty. The results showed the alpha diversity of intestinal microbiota in diabetes with frailty was lower. Collinsella and Butyricimonas were more abundant in diabetes with frailty. The functional characteristics showed that histidine metabolism, Epstein-Barr virus infection, sulfur metabolism, and biosynthesis of type Ⅱ polyketide products were upregulated in diabetes with frailty. Otherwise, butanoate metabolism and phenylalanine metabolism were down-regulated in diabetes with frailty. This research provides theoretical basic for exploring the mechanism of the gut microbiota on the occurrence and development of diabetes with frailty, and provides a basic for prevention and intervention of it.

Grayscale surface patterning using electrophoretic motion through a heterogeneous hydrogel material.

Chemical surface patterning can be an incredibly powerful tool in a variety of applications, as it enables precise spatial control over surface properties. But the equipment required to create functional surface patterns-especially "grayscale" patterns where independent control over species placement and density are needed-is often expensive and inaccessible. In this work, we leveraged equipment and methods readily available to many research labs, namely 3D printing and electroblotting, to generate controlled grayscale surface patterns. Three-dimensional-printed molds were used to cast polyacrylamide hydrogels with regions of variable polymer density; regions of low polymer density within the hydrogels served as reservoirs for proteins that were later driven onto a target surface using electrophoresis. This mechanism was used to deposit grayscale patterns of fluorescently labeled proteins, and the fluorescent intensity of these patterns was measured and compared to a theoretical analysis of the deposition mechanism.

The geriatric nutrition risk index versus the mini-nutritional assessment short form in predicting postoperative delirium and hospital length of stay among older non-cardiac surgical patients: a prospective cohort study.

BACKGROUNDS: Malnutrition has been shown to be associated with poor prognosis in older surgical patients. Several tools are available for detecting malnutrition. But little is known about their ability to assess risks of postoperative adverse outcomes. The study aimed to compare the ability of the Geriatric Nutritional Risk Index (GNRI) and the Mini-Nutritional Assessment Short Form (MNA-SF) in predicting postoperative delirium (POD) and length of stay (LOS) among older non-cardiac surgical patients. METHODS: Prospective study of 288 older non-cardiac surgical patients from the West China Hospital of Sichuan University. Preoperative nutritional status was assessed using the GNRI and MNA-SF, and patients were followed for the occurrence of POD and LOS. Multivariable logistic regression and linear regression analyses were used to identify predictors of these outcomes. The relative performance of the GNRI and MNA-SF as predictors of these outcomes were determined by Receiver Operating Characteristic curves (ROC) analyses and the area under the curve (AUC). RESULTS: Multivariable analysis revealed that preoperative malnutrition by the MNA-SF was significantly associated with POD. Linear regression analysis showed that preoperative low/high nutritional risk of the GNRI and malnutrition by the MNA-SF were independent predictors of prolonged LOS. Moreover, the area under the curve (AUC) of MNA-SF scores for POD was better than GNRI scores (AUC = 0.718, 95%CI: 0.64-0.80, P < 0.001 vs AUC = 0.606, 95%CI: 0.52-0.69, P = 0.019; Delong's test, P = 0.006), but the AUC of GNRI scores and MNA-SF scores have no significant difference when predicting prolonged LOS (AUC = 0.611, 95%CI: 0.54-0.69, P = 0.006 vs AUC = 0.533, 95%CI: 0.45-0.62, P = 0.421; Delong's test, P = 0.079). CONCLUSION: The MNA-SF was more effective than the GNRI at predicting the development of POD, but the two nutrition screening methods have similar performance in predicting prolonged LOS among older non-cardiac surgical patients.

Corticosteroids significantly increase cystatin C levels in the plasma by promoting cystatin C production in rats.

Background: Several studies have shown that non-renal factors such as corticosteroids may increase plasma cystatin C levels without affecting kidney function. However, the mechanisms underlying this are unclear. We hypothesized that corticosteroids may increase cystatin C levels in the plasma by promoting its production in tissues. In the present study, we aimed to test our hypothesis in rats by investigating the effect of corticosteroids on cystatin C production in tissues and the glomerular filtration rate (GFR), as measured by the gold standard method (i.e., inulin clearance). Results: Dexamethasone treatment was associated with much higher concentrations of cystatin C in all organ tissue homogenates tested. Dexamethasone increased plasma cystatin C levels in rats, without any decrease in renal inulin clearance. The impact of dexamethasone on plasma and organ tissue cystatin C levels was abolished by RU486, indicating the effect was glucocorticoid receptor-mediated. Conclusions: Our study provides direct evidence that corticosteroids may increase cystatin C levels in the plasma by promoting its production, without any decrease in GFR.

Memristors with diffusive dynamics as synaptic emulators for neuromorphic computing.

The accumulation and extrusion of Ca2+ in the pre- and postsynaptic compartments play a critical role in initiating plastic changes in biological synapses. To emulate this fundamental process in electronic devices, we developed diffusive Ag-in-oxide memristors with a temporal response during and after stimulation similar to that of the synaptic Ca2+ dynamics. In situ high-resolution transmission electron microscopy and nanoparticle dynamics simulations both demonstrate that Ag atoms disperse under electrical bias and regroup spontaneously under zero bias because of interfacial energy minimization, closely resembling synaptic influx and extrusion of Ca2+, respectively. The diffusive memristor and its dynamics enable a direct emulation of both short- and long-term plasticity of biological synapses, representing an advance in hardware implementation of neuromorphic functionalities.

Prevalence and Risk Factors of Acute Pulmonary Embolism in Patients with Lung Cancer Surgery.

Acute pulmonary embolism (PE) is one of the serious complications with high mortality after thoracic surgery. The authors aimed to determine the prevalence of PE events and evaluate additional risk factors for PE in patients with lung cancer surgery. Patients underwent lung cancer resections during January 2012 to July 2015 and had 30-day postoperative follow-up were included. Those with incomplete or miscoded data were excluded. The number of postoperative PE events was recorded retrospectively. Analyses were used to evaluate risk factors of PE during the hospitalization. The authors reviewed 11,474 patients who underwent surgery for lung cancer. The overall 30-day incidence of PE after thoracic surgery at their institution was 0.53%. The 30-day PE incidence without chemical prophylaxis was 0.57% (55/9,726) and the mortality rate was 10%. Multivariate analyses revealed that age over 66 (odds ratio [OR]: 1.09, 95% confidence interval [CI]: 1.05-1.12, p < 0.001), more extensive surgery than lobectomy (OR: 2.34, 95% CI: 1.28-4.25, p = 0.006) and stage IV of lung cancer (OR: 4.22, 95% CI: 1.50-11.9, p = 0.007) were associated with an increased risk of PE. Using these additional risk factors, based on readily available clinical characteristics, can help to risk-stratify patients and warrant extended chemical prophylaxis for patients to reduce the incidence of acute PE.