Batch Process Monitoring Based on Quality-Related Time-Batch 2D Evolution Information.

This paper proposed a quality-related online monitoring strategy based on time and batch two-dimensional evolution information for batch processes. In the direction of time, considering the difference between each phase and the steady part and the transition part in the same phase, the change trend of the regression coefficient of the PLS model is used to divide each batch into phases, and each phase into parts. The phases, the steady parts, and the transition parts are finally distinguished and dealt with separately in the subsequent modeling process. In the batch direction, considering the slow time-varying characteristics of batch evolution, sliding windows are used to perform mode division by analyzing the evolution trend of the score matrix T in the PLS model on the base of phase division and within-phase part division. Finally, an online monitoring model that comprehensively considers the evolution information of time and batch is obtained. In a typical batch operation process, injection molding is used as an example for experimental analysis. The results show that the proposed algorithm takes advantage of mixing the time-batch two-dimensional evolution information. Compared with the traditional methods, the proposed method can overcome the shortcomings caused by the single dimension analysis and has better monitoring results.

Programmed cell death-ligand 2: new insights in cancer.

Immunotherapy has revolutionized cancer treatment, with the anti-PD-1/PD-L1 axis therapy demonstrating significant clinical efficacy across various tumor types. However, it should be noted that this therapy is not universally effective for all PD-L1-positive patients, highlighting the need to expedite research on the second ligand of PD-1, known as Programmed Cell Death Receptor Ligand 2 (PD-L2). As an immune checkpoint molecule, PD-L2 was reported to be associated with patient's prognosis and plays a pivotal role in cancer cell immune escape. An in-depth understanding of the regulatory process of PD-L2 expression may stratify patients to benefit from anti-PD-1 immunotherapy. Our review focuses on exploring PD-L2 expression in different tumors, its correlation with prognosis, regulatory factors, and the interplay between PD-L2 and tumor treatment, which may provide a notable avenue in developing immune combination therapy and improving the clinical efficacy of anti-PD-1 therapies.

Efficacy and safety evaluation of combined therapies incorporating whole-brain radiotherapy in patients with brain metastases: a systematic review and meta-analysis.

BACKGROUND: Whole-brain radiotherapy (WBRT) is a standard and effective approach for brain metastases, but it is linked to neurocognitive complications, specifically issues related to the hippocampus. Innovative strategies are being explored to enhance outcomes. However, a consensus is yet to be reached in this field. Our aim is to investigate the efficacy and safety of WBRT combined with simultaneous integrated boost (SIB), memantine, and hippocampal avoidance (HA) techniques in treatment of brain metastases. METHODS: In this systematic review and meta-analysis, we comprehensively searched PubMed, MEDLINE, Embase, and Cochrane for studies reporting the efficacy and toxicity of WBRT-based combination therapies from inception to September 19, 2023. Data were pooled using random-effects models. Results were reported as risk ratios (RRs) and risk differences (RDs) for dichotomous outcomes, along with their 95% confidence intervals (CIs). Heterogeneity was evaluated using the I2 statistic. RESULTS: Among 2175 articles, 29 studies involving 3460 patients were included. The meta-analysis revealed that compared to WBRT alone, combination therapies significantly mitigated neurocognitive function decline (RD = -0.09, 95% CI [-0.18-0.01]; P = 0.03) and intracranial control failure (RR = 0.86, 95% CI [0.52-1.44]; P = 0.02), without increasing the risk of hippocampal recurrence or high-grade toxicities. Notably, HA-WBRT + SIB/memantine demonstrated improved neurocognitive outcomes and survival benefits. CONCLUSION: WBRT-based combination therapies demonstrate improved efficacy and comparable safety to WBRT alone, with specific emphasis on the effectiveness of HA-WBRT + Memantine and HA-WBRT + SIB in optimizing therapeutic outcomes for brain metastases.

High-Salt Diet Inhibits the Expression of Bmal1 and Promotes Atrial Fibrosis and Vulnerability to Atrial Fibrillation in Dahl Salt-Sensitive Rats.

BACKGROUND: Hypertension is a risk factor for atrial fibrillation (AF), and brain and muscle arnt-like protein 1 (Bmal1) regulate circadian blood pressure and is implicated in several fibrotic disorders. Our hypothesis that Bmal1 inhibits atrial fibrosis and susceptibility to AF in salt-sensitive hypertension (SSHT) and our study provides a new target for the pathogenesis of AF induced by hypertension. METHODS: The study involved 7-week-old male Dahl salt-sensitive that were fed either a high-salt diet (8% NaCl; DSH group) or a normal diet (0.3% NaCl; DSN group). An experimental model was used to measure systolic blood pressure (SBP), left atrial ejection fraction (LAEF), left atrial end-volume index (LAEVI), left atrial index (LAFI), AF inducibility, AF duration, and atrial fibrosis pathological examination and the expression of Baml1 and fibrosis-related proteins (TNF-α and α-SMA) in left atrial tissue. RESULTS: DSH increased TNF-α and α-SMA expression in atrial tissue, level of SBP and LAESVI, atrial fibrosis, AF induction rate, and AF duration, and decreased Bmal1 expression in atrial tissue, the circadian rhythm of hypertension, and level of LAEF and LAFI. Our results also showed that the degree of atrial fibrosis was negatively correlated with Bmal1 expression, but positively correlated with the expression of TNF-α and α-SMA. CONCLUSIONS: We demonstrated that a high-salt diet leads to circadian changes in hypertension due to a reduction of Bmal1 expression, which plays a crucial role in atrial fibrosis and increased susceptibility to AF in SSHT rats.

SIRT3/AMPK signaling pathway regulates lipid metabolism and improves vulnerability to atrial fibrillation in Dahl salt sensitive rats.

BACKGROUND: Hypertension may result in atrial fibrillation (AF) and lipid metabolism disorders. The Sirtuins3 (SIRT3) / AMP-activated protein kinase (AMPK) signaling pathway has the capacity to regulate lipid metabolism disorders and the onset of AF. We hypothesize that the SIRT3/AMPK signaling pathway suppresses lipid metabolism disorders, thereby mitigating salt-sensitive hypertension (SSHT)-induced susceptibility to AF. METHODS: The study involved 7-week-old male Dahl salt-sensitive that were fed either high-salt diet (8% NaCl; DSH group) or normal diet (0.3% NaCl; DSN group). Then DSH group were administered either oral metformin (MET, an AMPK agonist) or intraperitoneal injection of Honokiol (HK, a SIRT3 agonist). This experimental model allowed for the measurement of SBP, the expression levels of lipid metabolism-related biomarker, pathological examination of atrial fibrosis and lipid accumulation, as well as AF inducibility and AF duration. RESULTS: DSH decrease SIRT3, phosphorylation-AMPK and VLCAD expression, increased FASN and FABP4 expression and concentrations of FFA and TG, atrial fibrosis and lipid accumulation in atrial tissue, enhanced level of SBP, promoted AF induction rate and prolonged AF duration, which are blocked by MET and HK. Our results also showed that the degree of atrial fibrosis was negatively correlated with VLCAD expression, but positively correlated with the expression of FASN and FABP4. CONCLUSIONS: We have confirmed that high-salt diet can result in hypertension, associated atrial tissue lipid metabolism dysfunction. This condition is linked to the inhibition of the SIRT3/AMPK signaling pathway, which plays a significant role in the progression of susceptibility to AF in SSHT rats.

Prediction value of the genetic risk of type 2 diabetes on the amnestic mild cognitive impairment conversion to Alzheimer's disease.

Amnestic mild cognitive impairment (aMCI) and Type 2 diabetes mellitus (T2DM) are both important risk factors for Alzheimer's disease (AD). We aimed to investigate whether a T2DM-specific polygenic risk score (PRS sT2DM ) can predict the conversion of aMCI to AD and further explore the underlying neurological mechanism. All aMCI patients were from the Alzheimer's disease Neuroimaging Initiative (ADNI) database and were divided into conversion (aMCI-C, n = 164) and stable (aMCI-S, n = 222) groups. PRS sT2DM was calculated by PRSice-2 software to explore the predictive efficacy of the aMCI conversion to AD. We found that PRS sT2DM could independently predict the aMCI conversion to AD after removing the common variants of these two diseases. PRS sT2DM was significantly negatively correlated with gray matter volume (GMV) of the right superior frontal gyrus in the aMCI-C group. In all aMCI patients, PRS sT2DM was significantly negatively correlated with the cortical volume of the right superior occipital gyrus. The cortical volume of the right superior occipital gyrus could significantly mediate the association between PRS sT2DM and aMCI conversion. Gene-based analysis showed that T2DM-specific genes are highly expressed in cortical neurons and involved in ion and protein binding, neural development and generation, cell junction and projection, and PI3K-Akt and MAPK signaling pathway, which might increase the aMCI conversion by affecting the Tau phosphorylation and amyloid-beta (Aß) accumulation. Therefore, the PRS sT2DM could be used as a measure to predict the conversion of aMCI to AD.

Neurovascular coupling alterations in type 2 diabetes: a 5-year longitudinal MRI study.

INTRODUCTION: Respective alterations in resting-state brain neural activity and cerebral blood flow (CBF) in type 2 diabetes mellitus (T2DM) have been reported. However, their coupling alteration in T2DM remains largely unknown. RESEARCH DESIGN AND METHODS: Twenty-seven patients with T2DM aged 40-67 years and 36 well-matched healthy controls (HCs) underwent resting-state functional MRI (rs-fMRI) and arterial spin labeling (ASL) scans at two time points with a 5-year interval. Regional homogeneity (ReHo) and CBF were calculated from rs-fMRI and ASL, respectively. The standardized ReHo:CBF ratio (mReHo:mCBF ratio), the spontaneous neuronal activity per unit CBF supply, was compared between the two time points. Relationships between the mReHo:mCBF ratio and memory performance were analyzed. RESULTS: Over 5 years, decreased mReHo:mCBF ratios in patients with T2DM were mainly distributed in four regions, among which the left insula exhibited more severely decreased mReHo:mCBF ratio in patients with T2DM than in HCs, while the left postcentral gyrus, the right Rolandic operculum, and the right precentral gyrus showed no significant intergroup difference. Correlations between the mReHo:mCBF ratio and memory performance were also found in patients with T2DM. CONCLUSIONS: This study suggests that T2DM may accelerate neurovascular coupling impairment in specific brain regions (the left insula), contributing to memory decline. This study implies that the mReHo:mCBF ratio is a potential imaging marker for detecting neurovascular changes.